bromochloroacetic-acid and Dermatitis

The palmoplantar epidermis is a specialized area of the skin that undergoes high levels of mechanical stress. The palmoplantar keratinization and esophageal cancer syndrome, tylosis with esophageal cancer, is linked to mutations in RHBDF2 encoding the proteolytically inactive rhomboid protein, iRhom2. Subsequently, iRhom2 was found to affect palmoplantar thickening to modulate the stress keratin response and to mediate context-dependent stress pathways by p63. iRhom2 is also a direct regulator of the sheddase, ADAM17, and the antiviral adaptor protein, stimulator of IFN genes. In this perspective, the pleiotropic functions of iRhom2 are discussed with respect to the skin, inflammation, and the antiviral response.

Topics: ADAM17 Protein; Animals; Carrier Proteins; Dermatitis; Disease Models, Animal; Epidermis; Esophageal Neoplasms; Foot; Gene Expression Regulation; Hand; Host Microbial Interactions; Humans; Intracellular Signaling Peptides and Proteins; Keratinocytes; Keratins; Keratoderma, Palmoplantar; Mice; Mice, Knockout; Mutation; Signal Transduction; Skin Diseases, Viral; Transcription Factors; Tumor Suppressor Proteins

Topics: Dermatitis; Epidermis; Humans; Keratins

Topics: Antigens, Surface; Cell Adhesion; Cell Adhesion Molecules; Dermatitis; Epidermal Cells; Epidermis; Humans; Interferon-gamma; Keratins; Lymphocyte Activation; T-Lymphocytes

Topics: Antigens, Differentiation; Antigens, Surface; Cell Adhesion; Cell Adhesion Molecules; Dermatitis; Epidermal Cells; Glycoproteins; Humans; Keratins; Lymphocyte Function-Associated Antigen-1

Topics: Animals; Arachidonic Acids; Chemical Phenomena; Chemistry; Dermatitis; Humans; Keratins; Prostaglandins; Psoriasis; Skin; Ultraviolet Rays

Topics: Animals; Cathepsins; Chediak-Higashi Syndrome; Dermatitis; Fabry Disease; Keratins; Light; Lysosomes; Peptide Hydrolases; Phagocytosis; Sebaceous Glands; Skin; Skin Pigmentation; Vitamin A

Antipsoriatic agents have been shown to decrease skin levels of arachidonic acid and its metabolites including 12-monohydroxy-eicosatetranoic acid (12-HETE), and leukotriene B4 (LTB4). In addition, specific systemic and topical lipoxygenase inhibitors have been reported to be effective in the treatment of psoriasis. The objective of this study was to investigate the effect of a potent oral leukotriene biosynthesis inhibitor (MK886) in patients with chronic plaque psoriasis. Clinical response together with the changes of LTB4 levels in lesional skin biopsy specimens, and urinary leukotriene E4 (LTE4) excretion were evaluated. In addition, markers of inflammation, proliferation and keratinization were studied immunohistochemically. No change in clinical scores or lesional LTB4 levels were observed with a 10 1/3-day course of MK886. A statistically significant reduction in urinary LTE4 excretion was observed: mean LTE4 (ng/h) were 5.14 before treatment and 1.51 on day 11 with MK886; and 7.55 before treatment and 6.57 on day 11 with placebo treatment. Epidermal accumulation of polymorphonuclear leukocytes (PMN) tended to diminish in the MK886 treatment group. These results indicate that although a reduction (greater than 70%) in urinary LTE4 excretion was found, and a slight decrease of epidermal PMN accumulation was observed, no correlative changes in clinical scores or LTB4 levels in skin lesion were found with a short course of MK886.

Topics: Administration, Oral; Adult; Aged; Biomarkers; Biopsy; Dermatitis; Double-Blind Method; Female; Humans; Immunohistochemistry; Indoles; Keratins; Leukotriene Antagonists; Leukotriene B4; Male; Middle Aged; Psoriasis; Skin

Hyperproliferation of epidermal keratinocytes is a major histopathological feature of chronic Sarcoptes scabiei dermatitis. We investigated the immunohistochemical expression of several keratins in scabietic dermatitis in sheep and in the skin of healthy sheep, using a panel of commercially available anti-human antibodies for keratins. Keratins AE1/AE3 and 34BE12 were expressed in all epithelial structures in healthy skin. Keratin MNF116 was expressed in the stratum basale and in the three lowest layers of the stratum spinosum, in follicular epithelium and in apocrine glands. Keratin K5/6 expression was seen in the stratum basale, in the two lowest cell layers of the stratum spinosum, in the outer root sheath of hair follicles and in myoepithelial cells of apocrine glands. K14 expression was observed in the stratum basale, in locally extensive regions of the two lowest cell layers of the stratum spinosum, in the outer root sheath of hair follicles and in sebaceous glands. Immunolabelling of K19 antigen was confined to apocrine glands. In scabietic skin, immunolabelling of keratin 34BE12 was seen in all layers of hyperplastic stratum spinosum and stratum granulosum but was restricted to some locally extensive regions in hyperkeratotic and parakeratotic stratum corneum. Keratin MNF116 was widely labelled in all layers of hyperplastic stratum spinosum and stratum granulosum. There was expansive labelling of K5/6 keratin in all layers of hyperplastic stratum spinosum and in locally extensive regions of stratum granulosum, as well as in hyperkeratotic or parakeratotic stratum corneum. Expansive labelling of K14 keratin was detected in all layers of hyperplastic stratum spinosum and in the layers of the hyperplastic stratum granulosum. K5/6 and K14 keratins were also labelled in the inner root sheath of occasional hair follicles.

Topics: Animals; Dermatitis; Epidermis; Immunohistochemistry; Keratins; Sarcoptes scabiei; Scabies; Sheep; Sheep Diseases; Skin

Deficiency of the palmitoyl-acyl transferase ZDHHC13 compromises skin barrier permeability and renders mice susceptible to environmental bacterial infection and inflammatory dermatitis. It had been unclear how the lack of ZDHHC13 proteins resulted in cutaneous abnormalities. In this study, we first demonstrate that enzymatic palmitoylation activity, rather than protein scaffolding, by ZDHHC13 is essential for skin barrier integrity, showing that knock-in mice bearing an enzymatically dead DQ-to-AA ZDHHC13 mutation lost their hair after weaning cyclically, recapitulating knockout phenotypes of skin inflammation and dermatitis. To establish the ZDHHC13 substrates responsible for skin barrier development, we employed quantitative proteomic approaches to identify protein molecules whose palmitoylation is tightly controlled by ZDHHC13. We identified over 300 candidate proteins that could be classified into four biological categories: immunological disease, skin development and function, dermatological disease, and lipid metabolism. Palmitoylation of three of these candidates-loricrin, peptidyl arginine deiminase type III, and keratin fiber crosslinker transglutaminase 1-by ZDHHC13 was confirmed by biochemical assay. Palmitoylation was critical for in vivo protein stability of the latter two candidates. Our findings reveal the importance of protein palmitoylation in skin barrier development, partly by promoting envelope protein crosslinking and the filaggrin processing pathway.

Topics: Acyltransferases; Animals; Dermatitis; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Lipoylation; Membrane Proteins; Mice; Mice, Transgenic; Mutation; Protein Stability; Protein-Arginine Deiminase Type 3; Proteomics; Signal Transduction; Skin; Transglutaminases

The histologic features of abnormal spectacles in 60 snakes from the 5 families of Boidae, Colubridae, Elapidae, Pythonidae, and Viperidae are described in a retrospective study conducted on specimens submitted to a private diagnostic service during a period of 15 years. Fifty-two snakes had inflammatory reactions in the spectacle. The stroma and outer epithelium of the spectacle were the layers most often involved in inflammatory disease. Lesions of the outer epithelium included edema, hyperkeratosis, and granulocyte infiltration occasionally with bacterial colonies and fungal elements. The stroma had infectious agents and inflammatory reactions in vessels and between the collagen fibrils. The inner epithelium had varying degrees of hyperplasia and hypertrophy, but no infectious agents were seen. Infectious agents in these cases included mites, bacterial disease, fungal disease, or a combination of bacterial and fungal disease. Special stains identified the bacteria most commonly involved to be Gram-positive cocci. Thirteen snakes had dysecdysis of the spectacle. Of these, 5 displayed a concurrent inflammatory reaction of the spectacle, while the remaining 8 snakes had extra keratin layers on a spectacle with an otherwise normal appearance. These keratin layers were attached to serocellular crusts located on the inner surface of the periocular scales. The cause for dyskeratotic lesions of the spectacle was not always apparent, and concurrent acariasis, other forms of dermatitis, trauma, suboptimal husbandry, and visceral disease were considered possible contributing factors. It was notable that only 4% of the submitted cases were found to have spectaculitis and/or spectacular dysecdysis.

Topics: Animals; Dermatitis; Eyelid Diseases; Eyelids; Keratins; Molting; Retrospective Studies; Snakes

Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδ(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.

Topics: Animals; CD3 Complex; Cell Proliferation; Chronic Disease; Dendritic Cells; Dermatitis; Epidermis; Gene Deletion; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; Keratinocytes; Keratins; Lymphocyte Activation; Mice; Mice, Transgenic; Neutrophil Infiltration; Phenotype; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, G-Protein-Coupled; STAT3 Transcription Factor; T-Lymphocytes; Wnt Proteins

Metastatic Merkel cell carcinoma uncommonly presents with an unidentified primary tumour. We report a patient who first presented with lichenoid dermatitis and was found to have Merkel cell carcinoma involving lymph nodes with an unknown primary site. With the rising incidence of Merkel cell carcinoma, it is important to recognize unusual manifestations of this disease as they may become more common in the future.

Topics: Aged, 80 and over; Carcinoma, Merkel Cell; Carcinoma, Neuroendocrine; Carcinoma, Squamous Cell; CD56 Antigen; Comorbidity; Dermatitis; Fatal Outcome; Humans; Keratins; Lichenoid Eruptions; Lymphatic Metastasis; Male; Neoplasms, Unknown Primary; Phosphopyruvate Hydratase; Skin Neoplasms; Synaptophysin

Clear-cell acanthoma (CCA) has been reported to be a benign epidermal neoplasm; however, several authors have suggested alternative differentiation as well as other nosologic categories, including a reactive dermatosis. Fourteen CCAs, ten tricholemmomas, and seven cases of psoriasis were reviewed with conventional microscopy, periodic acid-Schiff stains, and immunohistochemical stains. Twelve of fourteen (86%) CCAs were associated with underlying or adjacent conditions. The CCAs stained immunohistochemically in a pattern similar to normal epidermis and psoriasis. Tricholemmomas stained in a distinctly different pattern with MNF116 and NGFR/p75. These cases demonstrate CCA in settings that reflect chronic inflammation, primarily scars and stasis dermatitis, and with an immunophenotype that parallels psoriasis. These findings support the contention that CCA does not show outer follicular sheath (tricholemmal) differentiation. Furthermore, these cases lend additional support to the contention that CCA represents a psoriasiform reaction pattern, which, in appropriately taken biopsies, usually has a demonstrable associated condition. Nonetheless, the precise nosology of this phenomenon has yet to be elucidated completely.

Topics: Acanthoma; Adult; Aged; Aged, 80 and over; Cicatrix; Dermatitis; Epidermis; Female; Hair Follicle; Hidradenitis Suppurativa; Humans; Hyperplasia; Keratins; Keratosis, Seborrheic; Male; Middle Aged; Molecular Weight; Neoplasms, Basal Cell; Nerve Tissue Proteins; Psoriasis; Receptors, Nerve Growth Factor; Skin; Skin Neoplasms

Inflammatory diseases at epithelial borders develop from aberrant interactions between resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of epithelial cells and immune cells and the sequence of their interactions in an inflammatory skin disease. Ubiquitous deficiency of the IkappaBalpha protein (Ikba(Delta)(/Delta)) as well as concomitant deletion of Ikba specifically in keratinocytes and T cells (Ikba(K5Delta/K5Delta lckDelta/lckDelta)) resulted in an inflammatory skin phenotype that involved the epithelial compartment and depended on the presence of lymphocytes as well as tumor necrosis factor and lymphotoxin signaling. In contrast, mice with selective ablation of Ikba in keratinocytes or lymphocytes showed inflammation limited to the dermal compartment or a normal skin phenotype, respectively. Targeted deletion of RelA from epidermal keratinocytes completely rescued the inflammatory skin phenotype of Ikba(Delta)(/Delta) mice. This finding emphasizes the important role of aberrant NF-kappaB activation in both keratinocytes and lymphocytes in the development of the observed inflammatory skin changes.

Topics: Abscess; Animals; Cell Communication; Dermatitis; Epidermis; Gene Deletion; I-kappa B Proteins; Keratinocytes; Keratins; Lymphotoxin-alpha; Mice; Mice, Mutant Strains; NF-KappaB Inhibitor alpha; Skin; T-Lymphocytes; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Skin inflammation is a complex process that involves interactions between various cell types residing in different skin compartments. Using mice with conditionally targeted I kappa B kinase 2 (IKK2) alleles, we have previously shown that epidermal keratinocytes can play a dominant role in the initiation of an inflammatory reaction. In order to investigate long-term consequences of IKK2 deletion in adult skin, we have generated mice with floxed IKK2 alleles in which expression of a Tamoxifen-inducible Cre recombinase construct is targeted to epidermal keratinocytes (K14-Cre-ER(T2)IKK2(fl/fl) mice). K14-Cre-ER(T2)IKK2(fl/fl) mice are born normally and do not show signs of a skin disease until the age of 6 months. Deletion of IKK2 can be observed after Tamoxifen application to the back skin or spontaneously, without Tamoxifen application, in mice older than 6 months. This deletion is accompanied by dramatic, localized skin changes that are characterized by invasion of inflammatory cells, hair follicle disruption, and pseudoepitheliomatous hyperplasia of the epidermis, but not by tumor formation. The hyperplastic epithelium shows increased phosphorylation of signal transducer and activator of transcription 3 and extracellular signal-regulated protein kinase 1/2, typical features of psoriatic epidermis. Our results identify a primary role for IKK2 in the development of skin inflammation and confirm its requirement for the maintenance of skin homeostasis.

Topics: Animals; Cell Differentiation; Cell Proliferation; Dermatitis; Gene Deletion; Hair Follicle; I-kappa B Kinase; Integrases; Keratin-14; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Skin; STAT3 Transcription Factor; Tamoxifen

How the inflammatory response is initiated has been well defined but relatively little is known about how such responses are resolved. Here we show that the D6 chemokine receptor is involved in the post-inflammatory clearance of beta-chemokines from cutaneous sites. After induction of inflammation by phorbol esters, wild-type mice showed a transient inflammatory response. However, in D6-deficient mice, an excess concentration of residual chemokines caused a notable inflammatory pathology with similarities to human psoriasis. These results suggest that D6 is involved in the resolution of the cutaneous inflammatory response.

Topics: Animals; Chemokine CXCL2; Chemokine Receptor D6; Chemokines; Chemokines, CC; Dermatitis; Female; Histocytochemistry; Inflammation; Keratins; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Proliferating Cell Nuclear Antigen; Psoriasis; Receptors, CCR10; Receptors, Chemokine; Skin; von Willebrand Factor

The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation.

Topics: Aging; Alopecia; Animals; Antigens, CD; Cadherins; Cell Differentiation; Cell Division; Dermatitis; Desmocollins; Desmosomes; Epidermis; Eyelids; Gene Targeting; Immunohistochemistry; Integrin beta4; Keratins; Ki-67 Antigen; Membrane Glycoproteins; Mice; Mice, Transgenic; Phenotype; Protein Isoforms; Recombination, Genetic; Skin Diseases

The expression of keratins and filaggrin by keratinocytes is a highly regulated process and depends on their state of differentiation and proliferation. As such, these proteins can be used as markers to determine if keratinocyte differentiation is normal. Mutant cpdm/cpdm mice develop a chronic skin disease characterized by epidermal hyperplasia and inflammation. Immunohistochemical staining for the basal keratins K5 and K14 revealed expression in the basal and suprabasal cell layers. The expression of K1 and K10 was reduced and limited to the outer layers of the stratum spinosum. Keratin 6 was expressed in the suprabasal layers of affected skin, and throughout all layers in severely affected skin. Filaggrin was present in the stratum granulosum which had variable thickness. These results indicate that the differentiation of keratinocytes in cpdm/cpdm mice was normal. The altered distribution and expression of keratins in comparison with the skin of control mice was the result of hyperproliferation.

Topics: Animals; Chronic Disease; Dermatitis; Filaggrin Proteins; Hyperplasia; Immunohistochemistry; Intermediate Filament Proteins; Keratinocytes; Keratins; Mice; Mice, Inbred C57BL; Mutation; Skin

Axillary granular parakeratosis is a recently described condition presenting with erythematous hyperkeratotic papules and plaques. We report on nine women and one man with eruptions not only localized to the axillae. Biopsy specimens were investigated by histology, immunohistochemistry, electron microscopy, immuno-electron microscopy, and in situ hybridization. In general, the epidermis was hyperplastic and showed a well preserved stratum granulosum. In the upper dermis a discrete perivascular CD4+ T-cell infiltrate was found, CD1+ dendritic cells were absent from the epidermis. The distribution pattern of the epidermal keratins (keratin 5/14, 1/10) and the expression of involucrin was regular. The horny layer was excessively thickened and parakeratotic. The nuclear remnants showed marginal chromatin condensation and were reactive for the nick-end labeling technique using TdT-mediated dUTP-biotin. The corneocytes were characteristically replete with basophilic granules which showed both ultrastructural features of keratohyalin granules and immunoreactivity for filaggrin. Loricrin was expressed irregularly in small L-granules. Granular parakeratotic cells revealed regular development of a cornified envelope while cell membranes and desmosomes remained undegraded. In conclusion, our studies on granular parakeratosis suggest a basic defect in processing of profilaggrin to filaggrin that results in a failure to degrade keratohyalin granules and to aggregate keratin filaments during cornification. Associated abnormalities of the cell surface structures and dysregulation of cornified envelope components may account for the retention hyperkeratosis. Further studies are necessary to clarify the etiology of this unique, acquired disorder of keratinization that localizes to intertriginous areas and body folds.

Topics: Adult; Aged; Antibodies, Monoclonal; Biopsy; Dermatitis; Epidermis; Female; Filaggrin Proteins; Humans; In Situ Nick-End Labeling; Keratinocytes; Keratins; Male; Microscopy, Immunoelectron; Middle Aged; Necrosis; Parakeratosis; Recurrence

The expression of SPRR (small proline-rich protein) was investigated in normal human skin and in diseased skin from patients with psoriasis, squamous cell carcinoma, basal cell epithelioma, naevus pigmentosus, ichthyosis vulgaris and several inflammatory skin diseases, by immunohistochemical staining. A polyclonal antibody was raised against a synthetic peptide for a C-terminal common region for SPRR1 and SPRR3. In immunoblot analysis, a positive band of 18 kDa was detected, which showed the presence of SPRR1 in human epidermal keratinocytes. In normal epidermis, positive staining for SPRR was observed in keratinocytes in the granular layer and the uppermost or two spinous cell layers, with no staining of the other spinous or basal layers. The staining was obvious at the cell periphery, weak at the cytoplasm, and absent in the nucleus. Staining was observed in several outer layers of the follicular infundibulum to the isthmus. No staining was detected in the inner root sheath of the hair follicles, hair matrix, sebaceous gland, eccrine gland, eccrine duct, melanocytes, Langerhans cells or fibroblasts. The arrectores pilorum, striated muscles, muscle layers of vessels, and myoepithelia of eccrine gland, were weakly stained. In psoriatic skin, stained keratinocytes were distributed in the spinous cell layers except for the basal layer. In ichthyosis vulgaris, SPRR was barely expressed in the uppermost living cell layers of the epidermis. In epidermolytic hyperkeratosis, degenerated squamous cells widely expressed SPRR. In Darier's disease, dyskeratotic cells were clearly stained. In squamous cell carcinoma, staining was observed in keratotic cells around horny pearls. In basal cell epithelioma, naevus pigmentosus, and malignant melanoma, the tumour cells or naevus cells were not stained. The distribution of SPRR was similar to that of involucrin in normal and several diseased skin, except for ichthyosis vulgaris. We conclude that SPRR is expressed in close association with epidermal differentiation in normal skin and skin diseases. The alteration of the expression of the proteins correlated to terminal differentiation, and differs from disease to disease.

Topics: Adult; Aged; Amino Acid Sequence; Cell Differentiation; Cornified Envelope Proline-Rich Proteins; Dermatitis; Epidermis; Female; Humans; Immunoblotting; Immunoenzyme Techniques; Keratins; Male; Membrane Proteins; Middle Aged; Molecular Sequence Data; Proteins; Psoriasis; Skin; Skin Diseases; Skin Neoplasms

Keratin K17, the myoepithelial keratin, is expressed in psoriasis but is not present in healthy skin. Psoriasis is associated with production of gamma interferon (IFN gamma), which induces the expression of keratin K17 by activating transcription factor STAT1. Our hypothesis states that the induction of K17 is specific for the inflammatory reactions associated with high levels of IFN gamma and activation of STAT1. One of the corollaries of the hypothesis is that the STAT1-activating cytokines should induce the expression of keratin K17, whereas those cytokines that work through other mechanisms should not. Furthermore, because the STAT activation pathway is dependent upon protein phosphorylation events, phosphorylation inhibitors should attenuate the induction of keratin K17, whereas protein phosphatase inhibitors should augment it. To test this hypothesis, we analyzed lesional samples of inflammatory diseases using immunofluorescence, transfected keratinocytes with K17 gene promoter DNAs in the presence of various cytokines, and followed nuclear translocation of STAT1 in keratinocytes using specific antibodies. Confirming the hypothesis, we found that K17 is induced in psoriasis and dermatitis caused by delayed type hypersensitivity, which are associated with high levels of IFN gamma, but not in samples of atopic dermatitis, which is not. Two cytokines, interleukin-6 and leukemia inhibitory factor, which can induce phosphorylation of STAT1, can also induce K17 expression, whereas interleukin-3, interleukin-4, interleukin-10, and granulocyte macrophage colony stimulating factor have no effect on K17 expression. As expected, staurosporine and genistein inhibited, whereas okadaic acid augmented, the induction of K17 by IFN gamma. Our data indicate that in inflammatory skin diseases, lymphocytes, through the cytokines they produce, differently regulate not only each other, but also keratin gene expression in epidermis one of their target tissues.

Topics: Cytokines; Dermatitis; Dermatitis, Atopic; DNA-Binding Proteins; Enzyme Inhibitors; Epidermis; Growth Inhibitors; Humans; Interferon-gamma; Interleukin-10; Interleukin-4; Interleukin-6; Keratins; Leukemia Inhibitory Factor; Lymphokines; Phosphoprotein Phosphatases; Promoter Regions, Genetic; Protein Kinase Inhibitors; Psoriasis; STAT1 Transcription Factor; Trans-Activators; Transcription, Genetic

Using indirect immunofluorescence assays on frozen tissue sections of skin from healthy subjects and subjects with inflammatory skin diseases, we found that intercellular adhesion molecule-1 (ICAM-1) was expressed in a cell surface pattern on epidermal keratinocytes at the site of lymphoid infiltration in cutaneous dermatoses. ICAM-1 was not expressed on epidermal keratinocytes in noninflamed skin. Its expression was not related solely to epidermal hyperproliferation, as hyperproliferative, tape-stripped epidermis did not express ICAM-1. We have reported previously that ICAM-1 expression on epidermal keratinocytes was upregulated by treatment with interferon gamma and that activated T lymphocytes bound to cultured epidermal keratinocytes in vitro by lymphocyte function associated-1 (LFA-1) molecules on T cells and ICAM-1 on epidermal keratinocytes. Taken together, these data suggest that upregulation of expression of ICAM-1 is an important feature of cutaneous inflammation.

Topics: Antigens, Surface; Cell Adhesion; Cell Adhesion Molecules; Cell Division; Dermatitis; Epidermal Cells; Humans; Keratins

Assessment of antikeratin antibodies (AKAs), using an indirect immunofluorescence technique with rat esophageal keratin as antigen, was performed in 14 patients with arthropathy and palmoplantar pustular eruptions, six of whom also had psoriasis vulgaris. Twelve patients had seronegative spondyloarthropathy. They were all AKA negative. Two patients had classical seropositive-erosive rheumatoid arthritis (RA), and were both AKA positive. This suggests that AKA is not related to the arthropathy associated with pustulosis palmoplantaris or psoriasis, or to the presence of pustular eruptions on the palms and soles. The finding of AKA in RA is in keeping with previous findings.

Topics: Aged; Autoantibodies; Dermatitis; Female; Humans; Immunoglobulin G; Joint Diseases; Keratins; Male; Middle Aged; Psoriasis

Pemphigus foliaceus is an uncommon dermatologic disorder occurring in several species and has been reported in horses during the past decade. An ultrastructural analysis of affected skin of horses presenting to our clinics has revealed early cytopathologic features of pemphigus-like disease, some of which closely resemble pemphigus foliaceus in the human, calve, and guinea pig. Prior to complete acantholysis and bullae formation, the intercellular spaces enlarged, but intercellular bridges and desmosomes remained intact. A novel finding was presence of aggregates of electron dense granular material which were seen in intercellular spaces of the epidermal basal cell layer, and may represent antigen-autoantibody complexed material or deranged cement substances. Other changes preceding acantholysis consisted of mild dyskeratosis, reduction of peripheral tonofilaments, enlargement of rough endoplasmic reticula, cytoplasmic vacuolization, and mitochondrial damage in epidermal cells. In more severe lesions where bullae were present and acantholysis was observed, bacterial invasion and leucocytic infiltration were evident in all epidermal layers, and corneal cells displayed cytoplasmic vacuolization and retention of nuclei. Basal cells remained intact, though intercellular spaces were enlarged on apical and lateral boundaries. The pathogenesis of this disease in the horse appeared morphologically similar to a pemphigus autoimmune disorder and its variants in other species, and morphologic evidence is provided to suggest that some cellular metabolic derangements may be concurrent with the extracellular events or cell peripheral changes that precede acantholysis and bullae formation.

Topics: Animals; Autoimmune Diseases; Corneal Diseases; Dermatitis; Epidermal Cells; Female; Horse Diseases; Horses; Keratins; Male; Pemphigus

We have investigated the immunoperoxidase staining pattern in the epidermis and dermal infiltrates of highly inflamed portions of psoriatic lesions, selecting for biopsy early pinpoint lesions or margins of active plaque lesions. We found positive intercellular staining for HLA-DR antigens in localized areas of the epidermis in about half of the patients tested. In contrast, OKT6 antigen was found only on the dendritic cells in the epidermis and dermis in all cases. These findings support the hypothesis that an active cellular immune reaction involving the epidermis, possibly associated with the expression of HLA-DR antigens on keratinocytes, occurs in the highly inflamed areas of psoriatic lesions, particularly in early pinpoint lesions or at the edges of spreading plaque lesions.

Topics: Dermatitis; Epidermal Cells; Epidermis; HLA-D Antigens; HLA-DR Antigens; Humans; Immunoenzyme Techniques; Keratins; Psoriasis

We report twenty-five patients with the acquired immunodeficiency syndrome (AIDS) and interface dermatitis. Patients with AIDS and interface dermatitis had numerous opportunistic and herpetic infections. Nearly all patients were receiving at least one medication prior to the development of their rash and many were clinically thought to have a drug eruption. When compared to skin biopsy specimens from non-AIDS patients with drug eruptions, specimens from patients with AIDS and interface dermatitis demonstrated a greater degree of vacuolar change, the frequent occurrence of necrotic keratinocytes, often in clumps, and the absence of eosinophils and polymorphonuclear leukocytes in the dermal infiltrates. Histologic and clinical features of our patients with AIDS and interface dermatitis are presented and contrasted with other interface dermatitides. Systemic and cutaneous immune abnormalities in patients with AIDS may be relevant to the pathogenesis of this interface process.

Topics: Acquired Immunodeficiency Syndrome; Adult; Biopsy; Dermatitis; Epidermal Cells; Female; Humans; Keratins; Male; Neutrophils; Skin; Vacuoles

We have identified a novel IgG antikeratin autoantibody in the serum of a Brazilian pemphigus foliaceus patient (Cascas-42). This antibody is specific for the 59 kD acidic murine keratin and its 56.5 kD human counterpart (Moll's catalogue #10), and is distinct from the pemphigus antibody system. Antikeratin autoantibodies present in the Cascas-42 serum were purified by affinity chromatography with a 59 kD murine keratin-agarose column (IAP-Cascas-42 antibodies). The specificity of the IAP-Cascas-42 antibodies was tested by indirect immunofluorescence and immunoelectron microscopy against epidermal cryosections, trypsin-dissociated keratinocytes, and epidermal cell cultures. The serum was also tested with extracts from unlabeled and surface 125I-labeled keratinocytes (Iodo-Gen method) by immunoblot analysis of one- and two-dimensional polyacrylamide gel electrophoresis. The IAP-Cascas-42 antibodies bind the intercellular spaces of murine epidermis, and the cell surfaces of viable, dissociated murine keratinocytes, as well as murine epidermal cells in culture by immunofluorescence and immunoelectron microscopy. These autoantibodies did not stain cytoplasmic keratins and did not react with parallel human epidermal substrates. The Cascas-42 serum identified the 59 kD murine acidic keratin and its 56.5 kD human counterpart in epidermal extracts by two-dimensional polyacrylamide gel electrophoresis and immunoblot analysis. In addition, surface radioiodination of viable murine keratinocytes selectively labeled the 59 kD keratin suggesting that a domain of this molecule is exposed on the cell surface. The 125I-labeled 59 kD keratin was also recognized by the Cascas-42 serum by immunoblotting and autoradiography. These studies suggest that in murine epidermis, the 59 kD keratin is a transmembrane protein with an extracellular domain recognized by the IAP-Cascas-42 antibodies.

Topics: Animals; Autoantibodies; Dermatitis; Epidermal Cells; Epidermis; Extracellular Space; Fluorescent Antibody Technique; Humans; Immunologic Techniques; Iodine Radioisotopes; Keratins; Mice; Molecular Weight; Pemphigus

The L1 antigen is a major cytosol component of human granulocytes that may also be expressed by macrophages and epithelial cells. Its epidermal and dermal occurrence was investigated in formalin-fixed routine biopsy material from eleven different inflammatory skin disorders. Localization was performed with a rabbit antiserum to L1 applied in an unlabeled antibody peroxidase-antiperoxidase method. L1 antigen was not found in normal skin except in epithelial cells of pilosebaceous units. However, epidermal L1 antigen was demonstrated in every biopsy specimen from lupus erythematosus, lichen planus, dermatitis herpetiformis, and atopic dermatitis, whereas granuloma annulare test results were usually negative. The occurrence of dermal L1 antigen depended on the composition of the inflammatory infiltrate; specimens rich in neutrophilic granulocytes (e.g., dermatitis herpetiformis) were particularly strongly stained. Extracellular dermal staining was also seen, especially in areas adjacent to accumulation of positive leukocytes. The varying epidermal occurrence of L1 antigen in skin diseases probably signified different degrees of proliferative activity of the epithelial cells and could apparently not be ascribed to uptake from the dermis.

Topics: Adolescent; Antigens, Surface; Child; Child, Preschool; Dermatitis; Epidermis; Epithelium; Granuloma; Histocompatibility Antigens Class II; HLA-DR Antigens; Humans; Infant; Keratins; Leukocyte L1 Antigen Complex; Skin

Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

Topics: Dermatitis; Epidermal Cells; Epidermis; HLA-D Antigens; HLA-DR Antigens; Humans; Interferon-gamma; Keratins; Langerhans Cells; Macrophages; Psoriasis; Skin; T-Lymphocytes

Topics: Antibodies, Monoclonal; Dermatitis; Histiocytosis, Langerhans-Cell; Histocytochemistry; Humans; Hypersensitivity, Delayed; Immunochemistry; Keratins; Skin Diseases; Skin Neoplasms; T-Lymphocytes

An experimental study concerning the effect of acute and chronic irritation on corneocytes was made in relation to cell number, size, and shape. Corneocytes from skin acutely irritated with a rough towel differed from those of normal skin: There was about a 60% decrease in the count and the corneocytes were 14% smaller in size on day 1 of the experiment. These parameters became normal in count and size after 10 days and 5 days, respectively. Concerning the morphological classification of cell outlines, there was no significant difference between the experimental and control groups except for slightly increased numbers of irregular cells in the experimental group. For the chronic irritation study, subjects were scrub nurses who had worked in the operating room for more than 3 years; ward nurses were used as a control group. Corneocytes from scrub nurses differed from those of the nonirritated skin of ward nurses; the number was twice as high on day 1 of the experiment. Two and four days later, the cell number markedly decreased and was similar to that in the control group. Throughout the experimental period, the surface of the corneocytes was 15% smaller in the experimental group than in the control group. There was no significant difference between the two groups with regard to corneocyte morphology.

Topics: Adult; Cell Count; Dermatitis; Epidermis; Female; Hand Disinfection; Humans; Keratins; Male; Skin

Topics: Acid Phosphatase; Animals; Cathepsins; Chediak-Higashi Syndrome; Cyclic AMP; Dermatitis; Fabry Disease; Humans; Keratins; Lupus Erythematosus, Systemic; Lysosomes; Psoriasis; Skin; Ultraviolet Rays; Vacuoles; Vitamin A Deficiency

Topics: Animals; Antigen-Antibody Reactions; Caseins; Cattle; Cyanides; Dermatitis; Dermatitis, Allergic Contact; Dermatitis, Atopic; Erythema; gamma-Globulins; Gelatin; Hydrogen-Ion Concentration; Keratins; Nickel; Proteins; Research; Serum Albumin; Serum Albumin, Bovine; Sulfides; Toxicology

Topics: Alopecia; Alopecia Areata; Dermatitis; Dermatitis, Atopic; Dermatitis, Seborrheic; Dermatology; Humans; Keratins; Mercury; Nails; Ointments; Pigmentation; Psoriasis