lipoteichoic-acid and Dermatitis--Atopic

Atopic Dermatitis is an inflammatory skin disease associated with broad defects in skin barrier function caused by increased levels of type-2 cytokines (IL-4 and IL-13) that repress keratinocyte (KC) differentiation. Although crucial in mediating allergic disease, the mechanisms for gene repression induced by type-2 cytokines remain unclear. In this study, we determined that gene repression requires the master regulator of the epidermal differentiation program, p63. We found that type-2 cytokine-mediated inhibition of the expression of genes involved in early KC differentiation, including keratin 1, keratin 10, and DSC-1, is reversed by p63 blockade. Type-2 cytokines, through p63, also regulate additional genes involved in KC differentiation, including CHAC-1, STC2, and CALML5. The regulation of the expression of these genes is ablated by p63 small interfering RNA as well. In addition, we found that IL-4 and IL-13 and Staphylococcus aureus lipoteichoic acid work in combination through p63 to further suppress the early KC differentiation program. Finally, we found that IL-4 and IL-13 also inhibit the activity of Notch, a transcription factor required to induce early KC differentiation. In conclusion, type-2 cytokine-mediated gene repression and blockade of KC differentiation are multifactorial, involving pathways that converge on transcription factors critical for epidermal development, p63 and Notch.

Topics: Cell Differentiation; Cells, Cultured; Dermatitis, Atopic; Desmocollins; Epigenetic Repression; Gene Knockdown Techniques; Humans; Interleukin-13; Interleukin-4; Keratin-1; Keratin-10; Keratinocytes; Lipopolysaccharides; Primary Cell Culture; Receptors, Notch; Signal Transduction; Skin; Staphylococcus aureus; STAT6 Transcription Factor; Teichoic Acids; Transcription Factors; Tumor Suppressor Proteins

Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, up-regulates inflammatory cytokine production through the toll-like receptor 2 (TLR2) signaling pathway, and also contributes to anti-inflammatory responses against immune cells stimulated by lipopolysaccharides. In the current study, we examined the effects of LTAs isolated from Staphylococcus aureus (aLTA) and Lactobacillus plantarum (pLTA) on the aggravation and alleviation of atopic dermatitis (AD). aLTA strongly induced CCL2 production in THP-1 cells. CCL2 was regulated by the TLR2 pathway including the activation of IRAK2, NF-κB and JNK. CCL2 induced Th2 polarization of CD4+T cells through induction of interleukin (IL)-2, -4, and -5 and inhibition of interferon-gamma (IFN-γ). CCL2 levels and immunoglobulin E (IgE) production were increased in aLTA-injected mice. On the other hand, pLTA moderately affected CCL2 production and it inhibited aLTA-mediated CCL2 production. The serum levels of CCL2 and IgE were inhibited by pLTA pre-injection followed by aLTA reinjection, which resulted in the alleviation of irritant contact dermatitis (ICD) symptoms. Our results suggest that S. aureus infection causes an increase in CCL2 production, and may exacerbate atopic dermatitis (AD)-like symptoms through the excessive IgE production. Alternatively, pLTA alleviated AD-like symptoms by inhibiting aLTA-induced CCL2 and IgE production.

Topics: Animals; Dermatitis, Atopic; Lactobacillus plantarum; Lipopolysaccharides; Mice; Staphylococcus aureus; Teichoic Acids

The innate immune complement system helps clear invading pathogens by forming membrane attack complexes (MACs) on their surface. Abnormal activation of the complement system may aggravate atopic dermatitis (AD) symptoms in AD patients. Here, we investigated the anti-AD effects of LTAs isolated from Lactobacillus plantarum (pLTA) and Staphylococcus aureus (aLTA) by examination of complement regulatory proteins (CRPs). Combination treatment with pLTA and aLTA increased CD55 and CD59 production in HaCaT cells. The regulation of CD55 and CD59 was mediated by p38 mitogen-activated protein kinase (p38) signaling pathways in pLTA- and aLTA-treated cells. Complement-dependent cytotoxicity (CDC) and bactericidal assays revealed that combination treatment with pLTA and aLTA down-regulated the complement system. In experiments using an irritant contact dermatitis (ICD)-induced mouse model, the levels of MAC and C3 convertase (C3C) were lower in serum collected from pLTA- and aLTA-injected mice than in serum from mice who were untreated or received pLTA or aLTA alone. Combination treatment also inhibited IgE and CCL2 levels in ICD mice. On the other hand, IFN-γ level was significantly increased, indicating that combination treatment switches the Th2 response to a Th1 response. Our results suggest that combination treatment with LTAs could be a good therapeutic approach to alleviate AD by reducing formation of MACs and inducing a Th1 response.

Topics: Animals; CD55 Antigens; CD59 Antigens; Cell Line; Dermatitis, Atopic; Humans; Lactobacillus plantarum; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Staphylococcus aureus; Teichoic Acids; Up-Regulation

Topics: Cell Differentiation; Dermatitis, Atopic; Humans; Keratinocytes; Lipopolysaccharides; Staphylococcus aureus; Teichoic Acids

The interplay between microbes and surface organs, such as the skin, shapes a complex immune system with several checks and balances. The first-line defense is mediated by innate immune pathways leading to inflammation. In the second phase specific T cells invade the infected organ, amplifying inflammation and defense. Consecutively, termination of inflammation is crucial to avoid chronic inflammation triggered by microbes, such as in patients with atopic dermatitis.. We aimed to elucidate how the Staphylococcus aureus-derived cell-wall component lipoteichoic acid (LTA) governs the second phase of immune responses when high concentrations of LTA access T cells directly through disrupted skin.. We analyzed the direct exposure of T cells to LTA in vitro. For in vivo analyses, we used fluorescein isothiocyanate contact hypersensitivity and ovalbumin-induced dermatitis as models for TH2-mediated cutaneous inflammation.. We observed that LTA potently suppressed T-lymphocyte activation in a Toll-like receptor 2-independent manner. LTA-exposed T cells did not proliferate and did not produce cytokines. Importantly, these T cells remained completely viable and were responsive to consecutive activation signals on subsequent removal of LTA. Thus LTA exposure resulted in temporary functional T-cell paralysis. In vivo experiments revealed that T-cell cytokine production and cutaneous recall responses were significantly suppressed by LTA.. We identified a new mechanism through which bacterial compounds directly but temporarily modulate adaptive immune responses.

Topics: Allergens; Animals; Cell Proliferation; Cytokines; Dermatitis, Atopic; Dermatitis, Contact; Fluorescein-5-isothiocyanate; Lipopolysaccharides; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; Ovalbumin; Staphylococcus aureus; T-Lymphocytes; Teichoic Acids; Toll-Like Receptor 2

Topics: Biopsy, Needle; Cell Movement; Cells, Cultured; Cytokines; Dermatitis, Atopic; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Keratinocytes; Lipopolysaccharides; Matrix Metalloproteinase 2; Oligopeptides; Phosphopeptides; Real-Time Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Teichoic Acids; Th2 Cells; Tissue Culture Techniques; Wound Healing

In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus (S. aureus). Resistance to bacterial skin infections, e.g. S. aureus, is based on the function of intact innate immune mechanisms in the epidermis, mainly provided by keratinocytes. Toll-like receptor (TLR)-2 recognizes components of S. aureus and is known to be expressed on keratinocytes. The aim of this study was to investigate intrinsic TLR-2 expression and cytokine secretion upon TLR-2 stimulation with peptidoglycan (PGN), lipoteichoic acid (LTA) and N-palmitoyl-S-[2,3-bis(palmitoyl)-(2RS)-propyl]-(R)cysteinyl-alanyl-glycine (Pam3Cys) in keratinocytes from patients with AD compared to healthy controls. Human primary keratinocytes (HPKs) were cultivated from hair follicles of patients with AD and non-atopic healthy controls and stimulated with Pam3Cys, LTA and PGN. TLR-2, TLR-1 and TLR-6 expression were investigated at the mRNA level. IL-6, IL-8, chemokine C-C motif ligand (CCL)-20 and MMP-9 production were studied at the protein level. TLR-2, TLR-1 and TLR-6 were expressed on both HPKs from patients with AD as well as healthy controls without significant differences between these groups. HPKs from patients with AD had an intrinsically reduced capacity to produce IL-6, IL-8, CCL-20 and MMP-9 and responded less to TLR-2 stimulation compared to HPKs from healthy controls. Our findings show evidence for intrinsic alterations in HPKs from patients with AD compared to healthy controls and diminished responses upon TLR-2 stimulation that might contribute to the enhanced susceptibility to skin infections with S. aureus.

Topics: Case-Control Studies; Chemokines; Cytokines; Dermatitis, Atopic; Gene Expression; Humans; In Vitro Techniques; Inflammation Mediators; Keratinocytes; Lipopolysaccharides; Lipoproteins; Matrix Metalloproteinase 9; Peptidoglycan; RNA, Messenger; Teichoic Acids; Toll-Like Receptor 1; Toll-Like Receptor 2; Toll-Like Receptor 6

The cutaneous colonization with Staphylococcus aureus represents a potent trigger factor of atopic dermatitis. Toll-like receptor (TLR)-2 and CD36 have been shown to play a pivotal role in the internalization of staphylococcal components.. To investigate the impact of TLR-2 ligands on cell surface protein expression in monocytes from wild type (WT) AD patients and TLR-2 R753Q polymorph AD patients.. CD36 expression was significantly less downregulated in TLR-2 polymorph AD patients compared to wild type AD patients upon stimulation with peptidoglycan (PGN) and lipoteichoic acid (LTA) and compared to healthy controls upon stimulation with PGN. Expression of CD86 was higher upon N-palmitoyl-S-[2,3-bis(palmitoyl)-(2RS)-propyl]-(R)cysteinyl-alanyl-glycine (Pam3Cys) stimulation in TLR-2 R753Q polymorph AD patients compared to wild type AD patients. Expression of CD80 and CD54 were unaffected.. The differences in CD36 expression in TLR-2 polymorph AD patients compared to wild type AD patients and healthy controls may be associated with an enhanced susceptibility to skin infections with S. aureus.

Topics: Case-Control Studies; CD36 Antigens; Dermatitis, Atopic; Disease Susceptibility; Humans; Ligands; Lipopolysaccharides; Monocytes; Peptidoglycan; Polymorphism, Single Nucleotide; Skin; Staphylococcal Skin Infections; Staphylococcus aureus; Teichoic Acids; Toll-Like Receptor 2

Bacterial infection with Staphylococcus aureus is a known trigger for worsening of atopic dermatitis (AD); the exact mechanisms by which bacterial infection worsens dermatitis are unknown.. We sought to characterize the amounts of the biologically active bacterial lipoprotein lipoteichoic acid (LTA) in infected AD lesions.. Eighty-nine children with clinically impetiginized lesions of AD were enrolled in this study. A lesion was graded clinically by using the Eczema Area and Severity Index (EASI), wash fluid obtained from the lesion for quantitative bacterial culture, and measurement of LTA and cytokines. The staphylococcal isolate was tested for antibiotic susceptibilities. The patients were treated with a regimen that included topical corticosteroids and systemic antibiotics, and the lesion was reanalyzed after 2 weeks.. S aureus was identified in 79 of 89 children enrolled in the study. The bacterial colony-forming unit (CFU) counts correlated with the EASI lesional score (P = .04). LTA levels as high as 9.8 mug/mL were measured in the wash fluid samples, and the amounts correlated with the lesional EASI scores (P = .01) and S aureus CFU (P < .001). Approximately 30% of clinically impetiginized AD lesions contained greater than 1 mug/mL LTA, amounts that exert effects on various cell types in vitro. Moreover, injection of skin tissue ex vivo with amounts of LTA found in AD lesions resulted in epidermal cytokine gene expression.. Pharmacologic levels of LTA are found in many infected atopic dermatitis lesions.

Topics: Child; Child, Preschool; Colony Count, Microbial; Dermatitis, Atopic; Eczema; Humans; Infant; Interleukin-8; Lipopolysaccharides; Severity of Illness Index; Skin; Staphylococcal Skin Infections; Staphylococcus aureus; Teichoic Acids; Tumor Necrosis Factor-alpha

In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. The pattern recognition receptor toll-like receptor (TLR)-2 recognizes components of S. aureus, for example, lipoteichoic acid (LTA) and peptidoglycan (PGN) and, therefore, might be crucial in the pathogenesis and flare-ups of AD.. To investigate TLR-2 expression and cytokine secretion in macrophages from patients with AD compared to healthy controls upon TLR-2 stimulation with PGN, LTA and Pam3Cys.. Macrophages were cultivated from highly purified peripheral blood monocytes of AD patients and nonatopic healthy controls and stimulated with PGN, LTA and Pam3Cys in a time and dose-dependent manner. Afterwards, TLR-2 expression and cytokine secretion were measured on protein and mRNA level. TLR-1 and TLR-6 expression were investigated on the mRNA level. Immunohistochemical stainings from punch biopsies were performed to investigate TLR-2 expression in skin macrophages.. We could clearly show that macrophages from patients with AD expressed significantly less TLR-2, whereas the expression pattern of TLR-1 and TLR-6 were not altered. Macrophages had a reduced capacity to produce pro-inflammatory cytokines such as IL-6, IL-8 and IL-1beta after stimulation with TLR-2 ligands.. Our findings clearly show an impaired TLR-2 expression and functional differences of TLR-2-mediated effects on macrophages of AD patients compared to healthy controls which might contribute to the enhanced susceptibility to skin infections with S. aureus in AD.

Topics: Cells, Cultured; Cytokines; Dermatitis, Atopic; Humans; Lipopolysaccharides; Macrophages; Peptidoglycan; Skin; Staphylococcus aureus; Teichoic Acids; Toll-Like Receptor 2

Antigen-presenting dendritic cells may play an important role in the pathogenesis of inflammatory skin diseases, including atopic dermatitis. Oregonin is demonstrated to have anti-inflammatory and anti-oxidant effects. The present study was designed to assess the effect of oregonin against stimulated responses in dendritic cells of mouse bone marrow and spleen. Dendritic cells exposed to lipopolysaccharide, lipoteichoic acid and IL-1beta exhibited increase in the production of IL-12 p70 and TNF-alpha, increase in the formation of reactive oxygen species and nitric oxide, and elevation of intracellular Ca2+ levels. Treatment of oregonin attenuated the microbial product- or IL-1beta-stimulated responses in dendritic cells in a dose-dependent manner. Oregonin revealed a significant inhibitory effect on the production of cytokine, the formation of reactive oxygen species and nitric oxide, and the change in intracellular Ca2+ levels in dendritic cells of bone marrow and spleen. The results show that oregonin seems to attenuate the stimulated cell responses, including cytokine production, in dendritic cells exposed to microbial products and IL-1beta. The findings suggest that oregonin may exert an inhibitory effect against the dendritic cell-mediated immune response.

Topics: Animals; Calcium; Cell Separation; Cell Survival; Cells, Cultured; Cytokines; Dendritic Cells; Dermatitis, Atopic; Diarylheptanoids; Female; Fluorescent Dyes; Fura-2; Interleukin-12; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nitrates; Nitrites; Reactive Oxygen Species; Teichoic Acids; Tumor Necrosis Factor-alpha

Atopic dermatitis (AD) is often complicated by an enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus. Toll-like receptors (TLR), especially TLR-2 recognizes cell wall components of S. aureus, e.g. lipoteichoic acid (LTA) and peptidoglycan (PGN). A heterozygous TLR-2 R753Q polymorphism occurs in a frequency of 11.5% in adult AD patients and has been shown to be associated with a severe phenotype of AD.. The aim of this study was to investigate the impact of TLR-2 agonists (LTA, PGN and Pam3Cys) on cytokine production in human monocytes from AD patients with the TLR-2 R753Q polymorphism compared with that of AD patients with 'wild type' TLR-2 and control individuals to elucidate the functional role of the TLR-2 R753Q polymorphism.. Monocytes from AD patients with the TLR-2 R753Q mutation produced significantly more IL-6 and IL-12 compared with that of AD patients with nonmutated TLR-2 upon stimulation with TLR-2 agonists.. We show for the first time functional differences in TLR-2 responsiveness of monocytes from AD patients with the TLR-2 R753Q mutation compared with wild type AD patients in a ligand-dependent manner.. Our data support the emerging concept that AD patients have a dysbalance in innate and acquired immunity. TLR-2 may be essential in the pathogenesis and maintenance of AD and may be involved in the enhanced susceptibility to skin infections with S. aureus and in a higher inflammatory response in patients with AD carrying the TLR-2 polymorphism.

Topics: Dermatitis, Atopic; Humans; Interleukin-12; Interleukin-6; Ligands; Lipopolysaccharides; Monocytes; Peptidoglycan; Polymorphism, Single Nucleotide; Staphylococcus aureus; Teichoic Acids; Toll-Like Receptor 2

Bacterial stimulation may serve to control atopic disorders such as atopic dermatitis (AD) through inducement of Th1 cell-mediated immune response. The lipoteichoic acid (LTA)-related molecule (okLTA) from streptococcal preparation, OK-432, has been shown to be a potent Th1 inducer through the action of IL-12. Examination was made of the therapeutic effects of this okLTA injected intra- and/or subcutaneously into AD-like lesions in NC/Nga mice, particularly in the vicinity of the suppressor of cytokine signaling (SOCS) regulatory pathways. Using immunohistochemical staining with IL-4/IL-12p40 and phosphorylated STAT6/p-STAT4 and RT-PCR for IL-4/IL-12p40, STAT6/STAT4 and mRNA expression and in situ hybridization of SOCS3 and 5, evaluation was made of the immunoregulatory effects of this okLTA in the treatment of spontaneous AD-like lesions in NC/Nga mice. Following the injection of okLTA, remarkable improvement in the lesions of NC/Nga mice was noted. In okLTA-treated skin, IL-12p40/p-STAT4 positive cellular infiltration was extensive while IL-4/p-STAT6 positive cell infiltration was seen to diminish considerably, compared to untreated NC mice. SOCS3 in situ expression in okLTA-treated mice was noted to be significantly less compared to untreated NC mice, in which the expression was prominent. SOCS5 in situ expression was rather, though not significantly, strong in okLTA-treated mice. okLTA treatment is clearly shown to induce Th1 cellular response and down-regulate immune response in the Th2 pathway through SOCS3 reduction in AD-like lesions of NC/Nga mice. The present results demonstrate that bacterial wall components such as okLTA should serve as an effective new therapeutic approach for treating AD.

Topics: Animals; Anti-Inflammatory Agents; Dermatitis, Atopic; Down-Regulation; Immunohistochemistry; In Situ Hybridization; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Models, Animal; Monocytes; Picibanil; STAT6 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Teichoic Acids; Th1 Cells; Th2 Cells; Up-Regulation

Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor-positive and -negative (PAF-R-positive and -negative) cells and PAF-R-deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R-positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R-deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R-expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis.

Topics: Animals; Calcium; Cell Line; Dermatitis, Atopic; Dinitrofluorobenzene; Drug Hypersensitivity; Drug Synergism; Humans; Hypersensitivity, Delayed; Inflammation; Interleukin-10; Lipopolysaccharides; Mice; Mice, Knockout; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, G-Protein-Coupled; Skin; Staphylococcal Infections; Staphylococcus aureus; Teichoic Acids; Th1 Cells; Th2 Cells

In the present study, the effects of the macrolide antibiotic, midecamycin (MDM), on the Th2 cytokine response induced by the Staphylococcus aureus products, staphylococcal enterotoxin B (SEB), lipoteichoic acid (LTA), and peptidoglycan (PEG), was investigated in human peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD). MDM inhibited SEB-induced mRNA expression of the Th2 cytokines interleukin-4 (IL-4) and IL-5 in PBMCs from patients with AD. Furthermore, MDM also suppressed LTA-induced or PEG-induced IL-5 mRNA expression in these patients. Inhibition of mRNA expression by MDM correlated with the synthesis of cytokines in PBMCs, indicating that MDM controls Th2 cytokine production. In addition, S. aureus strains isolated from skin lesions of patients with AD were particularly susceptible to MDM compared with gentamicin, which is used widely in Japan as an antibiotic ointment combined with steroid for topical application in AD. These results suggest that topical administration of MDM might be beneficial in AD lesions infected with S. aureus.

Topics: Adult; Anti-Bacterial Agents; Cytokines; Dermatitis, Atopic; Enterotoxins; Gene Expression Regulation; Gentamicins; Humans; Interleukin-4; Interleukin-5; Leucomycins; Lipopolysaccharides; Macrolides; Peptidoglycan; RNA, Messenger; Staphylococcus aureus; Teichoic Acids; Th2 Cells

We found previously that lipoteichoic acid (LTA) from Staphylococcus aureus has the ability to induce Th2 cytokine production by peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD). However, it is not known whether LTA can induce a Th2-dominant cytokine response in the skin of AD patients.. The purpose of this study was to determine the effects of LTA in mice sensitized percutaneously with a house dust mite antigen (MA) through barrier-disrupted skin, as an experimental animal model of AD.. Mice were sensitized with MA by a single topical application to barrier-disrupted abdominal skin. Seven days after the sensitization, the mice were challenged on the dorsal skin by LTA to elicit localized skin inflammation. The cytokine response in the dorsal skin was investigated by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistological analysis. The infiltration of inflammatory cells in the skin was also observed by histological staining.. Injection of LTA into the dorsal skin of MA-sensitized mice, which show a Th2-dominant cytokine response against the homologous antigen, increased the expression of mRNA for IFN-gamma, IL-4 and IL-5, but not IL-2. Immunohistological analysis demonstrated that levels of IFN-gamma, IL-4 and IL-5 transcripts corresponded with those of protein synthesis. In addition, the dorsal skin of MA-sensitized mice challenged with LTA showed significantly increased numbers of neutrophils, eosinophils, mononuclear cells and mast cells compared with control mice challenged with LTA.. These results suggest that LTA has the ability to induce localized Th2-prone dermatitis in an allergen-independent manner in the skin of AD patients and may explain the role of colonization with S. aureus in AD patients.

Topics: Allergens; Animals; Dermatitis, Allergic Contact; Dermatitis, Atopic; Female; Immunization; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Skin; Staphylococcus aureus; Teichoic Acids; Th2 Cells

Lipoteichoic acid (LTA) and peptidoglycan (PEG) from Staphylococcus aureus induced interleukin-5 (IL-5) production in human peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) but not in PBMC from healthy donors. The production of IL-5 induced by LTA or PEG was correlated with the expression of IL-5 mRNA in PBMC. Furthermore, the level of IL-5 production induced by treatment with both LTA and PEG from S. aureus was higher than that induced by the addition of each alone. These results suggest that LTA and PEG have an additive effect on IL-5 production in PBMC from AD patients and may explain the role of colonization with nontoxin-producing strains of S. aureus in these patients.

Topics: Adjuvants, Immunologic; Adult; Cell Wall; Cells, Cultured; Dermatitis, Atopic; Humans; Interleukin-5; Lipopolysaccharides; Lymphocytes; Peptidoglycan; Staphylococcus aureus; Teichoic Acids

Staphylococcus aureus has a peculiar ability to colonize the skin of patients with atopic dermatitis. We examined the possibility that this might be due to a specific ability of this pathogenic staphylococcus to adhere to atopic stratum corneum. We used an in vitro model to show that S aureus does have an unusual ability to adhere to atopic corneocytes when compared with corneocytes obtained from patients with other cutaneous diseases, including psoriasis. Protein A--a component of the staphylococcal cell wall--may be responsible in part for this adherence phenomenon. This trait did not extend to the other gram-positive bacteria tested.

Topics: Cell Division; Dermatitis, Atopic; Epidermal Cells; Epidermis; Humans; Hydrogen-Ion Concentration; Keratins; Lipopolysaccharides; Phosphatidic Acids; Skin; Staphylococcal Protein A; Staphylococcus aureus; Teichoic Acids; Temperature