interleukin-8 and Dermatitis--Allergic-Contact

interleukin-8 has been researched along with Dermatitis--Allergic-Contact* in 17 studies

Other Studies

17 other study(ies) available for interleukin-8 and Dermatitis--Allergic-Contact

ArticleYear
The transcriptome of hand eczema assessed by tape stripping.
    Contact dermatitis, 2022, Volume: 86, Issue:2

    No biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the gold standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin-tape strips for molecular investigations enable noninvasive investigations of HE.. By using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/morphological subtypes was investigated.. Thirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, nonlesional, and healthy skin. Total RNA was extracted and WTS was performed.. The largest molecular difference of HE patients with and without AD was found in nonlesional skin areas and included a downregulation of CXCL8 for HE patients without AD. Differences between allergic and irritant contact dermatitis included epidermal biomarkers such as EPHA1.. Skin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes.

    Topics: Adult; Aged; Biomarkers; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatitis, Irritant; Diagnosis, Differential; Down-Regulation; Exome Sequencing; Female; Hand Dermatoses; Humans; Interleukin-8; Male; Middle Aged; Receptor, EphA1; Skin; Specimen Handling; Surgical Tape; Transcriptome

2022
The modified IL-8 Luc assay, an in vitro skin sensitisation test, can significantly improve the false-negative judgment of lipophilic sensitizers with logK
    Archives of toxicology, 2021, Volume: 95, Issue:2

    False-negative judgment due to poor chemical solubility is a problem with in vitro skin sensitisation tests. Water-insoluble chemicals are typically dissolved in DMSO in most sensitisation tests but precipitate when diluted with medium beyond their solubility in water. Such tests lack procedures to rule out false-negative judgments due to poor solubility. The IL-8 Luc assay (OECD442E) is unique in that if chemicals do not dissolve at 20 mg/mL in medium and have no effect on IL-8 luciferase activity (IL8LA), they are classified as indeterminate. The purpose of the present study was to reduce the number of indeterminate chemicals and improve assay performance. The IL-8 Luc assay can simultaneously examine glyceraldehyde 3-phosphate dehydrogenase luciferase activity (GAPLA) and IL8LA, and thus we examined the correlation between the reduction of GAPLA (defined as Inh-GAPLA) and the reduction of propidium iodide (PI)-excluding cells for three sensitizers and three non-sensitizers. We observed a significant correlation between luciferase activity driven by the GAPDH promoter of THP-G8 cells and the number of viable cells. Furthermore, chemicals providing an Inh-GAPLA value below 0.8 always reduced the ratio of PI-excluding cells to less than 0.6. Using the modified criteria, indeterminate chemicals are judged as negative if they provide Inh-GAPLA values below 0.8. This modification reduced the number of indeterminate chemicals and increased specificity, highlighting the unique advantage of the IL-8 Luc assay.

    Topics: Allergens; Animal Testing Alternatives; Biological Assay; Cell Line; Dermatitis, Allergic Contact; False Negative Reactions; Gene Expression Regulation; Genes, Reporter; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Interleukin-8; Luciferases; Peptide Fragments; Promoter Regions, Genetic; Skin Tests; THP-1 Cells

2021
The IL-1 promoter-driven luciferase reporter cell line THP-G1b can efficiently predict skin-sensitising chemicals.
    Archives of toxicology, 2021, Volume: 95, Issue:5

    IL-1 functions as an essential pro-inflammatory mediator for the sensitisation of allergic contact dermatitis (ACD). However, studies conducted to date have typically used a limited number of haptens and examined their effects only on murine ACD or murine dendritic cells (DCs). It therefore remains unclear whether IL-1α and/or IL-1β is produced in ACD induced by haptens other than those commonly used in mouse ACD models, and whether they are essential for sensitisation leading to ACD in humans. In addition, it is unclear whether human DCs also produce IL-1α or IL-1β after stimulation by haptens in general. Here, we first demonstrated that 10 haptens (3 extreme, 1 strong, 3 moderate and 3 weak) increased both IL-1α mRNA and IL-1β mRNA expression by the human monocyte cell line THP-1, a commonly used surrogate of DCs in in vitro skin sensitisation tests. Next, we constructed an in vitro skin sensitisation test using a stable IL-1β reporter cell line, THP-G1b, and evaluated whether 88 haptens and 34 non-haptens increase IL-1β reporter activity. We found that 94% of 77 haptens evaluated after considering their applicability domain and solubility in the chosen media stimulated reporter activity. These studies demonstrated that most haptens, irrespective of their potency, increased IL-1β mRNA expression by THP-1 cells, confirming that human DCs also produce IL-1β after stimulation by most haptens. The luciferase assay using THP-G1b cells is thus another skin sensitisation test based on the adverse outcome pathway with reasonable performance.

    Topics: Allergens; Animal Testing Alternatives; Animals; Cell Line; Dendritic Cells; Dermatitis, Allergic Contact; Haptens; Humans; In Vitro Techniques; Interleukin-1alpha; Interleukin-8; Luciferases; Mice; Monocytes; Promoter Regions, Genetic; Skin; Skin Tests; THP-1 Cells

2021
Evaluation of in vitro testing strategies for hazard assessment of the skin sensitization potential of "real-life" mixtures: The case of henna-based hair-colouring products containing p-phenylenediamine.
    Contact dermatitis, 2019, Volume: 81, Issue:3

    Allergic contact dermatitis caused by henna-based hair-colouring products has been associated with adulteration of henna with p-phenylenediamine (PPD).. To develop a testing approach based on in vitro techniques that address key events within the skin sensitization adverse outcome pathway in order to evaluate the allergenic potential of hair-colouring products.. The following in vitro assays were used to test the sensitizing capacity of hair dye ingredients: the micro-direct peptide reactivity assay (mDPRA); the HaCaT keratinocyte-associated interleukin (IL)-18 assay; the U937 cell line activation test (U-SENS)/IL-8 levels; the blood monocyte-derived dendritic cell test; and genomic allergen rapid detection (GARD skin). Those techniques with better human concordance were selected to evaluate the allergenic potential of 10 hair-colouring products.. In contrast to the information on the label, chromatographic analyses identified PPD in all products. The main henna biomarker, lawsone, was not detected in one of the 10 products. Among the techniques evaluated by testing hair dye ingredients, the mDPRA, the IL-18 assay, GARD skin and the U-SENS correlated better with human classification (concordances of 91.7%-100%) and were superior to the animal testing (concordance of 78.5%). Thus, these assays were used to evaluate hair-colouring products, which were classified as skin sensitizers by the use of different two-of-three approaches.. Our findings highlight the toxicological consequences of, and risks associated with, the undisclosed use of PPD in henna-based "natural" "real-life" products.

    Topics: B7-2 Antigen; Biological Assay; Cell Line, Tumor; Chromatography, High Pressure Liquid; Dendritic Cells; Dermatitis, Allergic Contact; Hair Dyes; Humans; In Vitro Techniques; Interleukin-18; Interleukin-8; Keratinocytes; Naphthoquinones; Phenylenediamines

2019
Improved metal allergen reactivity of artificial skin models by integration of Toll-like receptor 4-positive cells.
    Contact dermatitis, 2019, Volume: 81, Issue:4

    Reconstructed human epidermis (RhE) is widely used to replace animal models in order to assess the proinflammatory and allergenic effects of chemicals. Unfortunately, RhE lacks proinflammatory responsiveness for metal haptens, which are the most prevalent human contact allergens, raising concerns about its reliability for predicting skin allergens.. To investigate whether this limitation of RhE might be attributable to a lack of functional expression of Toll-like receptor 4 (TLR4), which governs proinflammatory sensitivity to nickel and cobalt.. RhE, dendritic cell (DC)-containing RhE and full-thickness skin equivalent (FTSE) were compared regarding their proinflammatory responsiveness to metal allergens.. The incorporation of dermal fibroblasts was sufficient to confer metal sensitivity to RhE. Unlike keratinocytes, normal human fibroblasts expressed high levels of TLR4 mRNA and induced interleukin-8 expression upon stimulation with nickel or cobalt. Consistently, dermal isolates from FTSE expressed considerable amounts of TLR4 mRNA, whereas RhE or epidermis isolated from FTSE, normal human epidermis or inflamed human epidermis failed to express TLR4. Similarly, co-culture with TLR4-positive DCs bestowed RhE with proinflammatory responsiveness to metals.. Our data suggest that FTSE or DC/RhE co-culture models can circumvent the shortcomings of RhE assays, and combine the benefits of complex and monoculture-based test systems in a single assay.

    Topics: Cobalt; Coculture Techniques; Dendritic Cells; Dermatitis, Allergic Contact; Fibroblasts; Humans; Inflammation; Interleukin-8; Keratinocytes; Metals; Models, Biological; Nickel; RNA, Messenger; Skin; Skin, Artificial; Toll-Like Receptor 4

2019
Cytokine patterns in vitro, in particular IL-5/IL-8 ratio, to detect patients with nickel contact allergy.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2018, Volume: 32, Issue:9

    Patch test (PT) is the gold standard to reveal nickel (Ni) allergy. In vitro tests are under discussion. We aimed to establish a cytokine based in vitro assay to detect Ni sensitization.. From 15 patients with positive (13f, 42-78 years) and 15 with negative PT to Ni (controls, 3f, 31-82 years) within a consecutive patient series, peripheral blood mononuclear cells (PBMC) were obtained. Six-day stimulation with three concentrations of NiSO. Twelve of fifteen Ni PT-positive patients also had positive LTT, and all control patients were PT and LTT negative. The mean SI differed between Ni allergics and controls (P < 0.01). Upon Ni stimulation, PBMC of the allergic patients showed (i) enhanced IL-5 response (P < 0.0001) and (ii) reduced IL-8 production (P < 0.01). The IL-5/IL-8-ratio best distinguished allergics from non-allergics in all three Ni concentrations with a sensitivity and specificity of 93%.. Assessment of the ratio of Ni-induced IL-5 and reduced IL-8 production in vitro is a helpful tool for a better characterization of Ni-allergic patients.

    Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cells, Cultured; Cytokines; Dermatitis, Allergic Contact; Female; Humans; Interleukin-5; Interleukin-8; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Middle Aged; Nickel; Patch Tests; Primary Cell Culture; Sensitivity and Specificity

2018
Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis.
    The Journal of pharmacology and experimental therapeutics, 2018, Volume: 365, Issue:3

    Phytocannabinoids modulate inflammatory responses by regulating the production of cytokines in several experimental models of inflammation. Cannabinoid type-2 (CB

    Topics: Anti-Inflammatory Agents; Arachidonic Acids; Cannabidiol; Cell Line; Chemokine CCL8; Dermatitis, Allergic Contact; Endocannabinoids; Humans; Interleukin-6; Interleukin-8; Polyunsaturated Alkamides; Tumor Necrosis Factor-alpha

2018
Transferability and within- and between-laboratory reproducibilities of EpiSensA for predicting skin sensitization potential in vitro: A ring study in three laboratories.
    Journal of applied toxicology : JAT, 2018, Volume: 38, Issue:9

    The epidermal sensitization assay (EpiSensA) is an in vitro skin sensitization test method based on gene expression of four markers related to the induction of skin sensitization; the assay uses commercially available reconstructed human epidermis. EpiSensA has exhibited an accuracy of 90% for 72 chemicals, including lipophilic chemicals and pre-/pro-haptens, when compared with the results of the murine local lymph node assay. In this work, a ring study was performed by one lead and two naive laboratories to evaluate the transferability, as well as within- and between-laboratory reproducibilities, of EpiSensA. Three non-coded chemicals (two lipophilic sensitizers and one non-sensitizer) were tested for the assessment of transferability and 10 coded chemicals (seven sensitizers and three non-sensitizers, including four lipophilic chemicals) were tested for the assessment of reproducibility. In the transferability phase, the non-coded chemicals (two sensitizers and one non-sensitizer) were correctly classified at the two naive laboratories, indicating that the EpiSensA protocol was transferred successfully. For the within-laboratory reproducibility, the data generated with three coded chemicals tested in three independent experiments in each laboratory gave consistent predictions within laboratories. For the between-laboratory reproducibility, 9 of the 10 coded chemicals tested once in each laboratory provided consistent predictions among the three laboratories. These results suggested that EpiSensA has good transferability, as well as within- and between-laboratory reproducibility.

    Topics: Activating Transcription Factor 3; Cells, Cultured; Dermatitis, Allergic Contact; Epidermis; Gene Expression Regulation; Genetic Markers; Glutamate-Cysteine Ligase; HSP40 Heat-Shock Proteins; Humans; Interleukin-8; Irritants; Keratinocytes; Laboratory Proficiency Testing; Observer Variation; Predictive Value of Tests; Reproducibility of Results; Risk Assessment; Skin Irritancy Tests

2018
New attempts to improve in vitro diagnosis of contact allergy are still far from regular clinical practice.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2018, Volume: 32, Issue:10

    Topics: Cytokines; Dermatitis, Allergic Contact; Humans; Interleukin-5; Interleukin-8; Nickel

2018
The performance of an in vitro skin sensitisation test, IL-8 Luc assay (OECD442E), and the integrated approach with direct peptide reactive assay (DPRA).
    The Journal of toxicological sciences, 2018, Volume: 43, Issue:12

    Topics: Animal Testing Alternatives; Biological Assay; Dermatitis, Allergic Contact; Genes, Reporter; Glyceraldehyde-3-Phosphate Dehydrogenases; Haptens; Humans; Interleukin-8; Luciferases; Peptides; Skin Tests; THP-1 Cells

2018
Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators.
    Contact dermatitis, 2013, Volume: 68, Issue:6

    Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll-like receptor (TLR)-4.. Here, we studied an extended panel of transition metals neighbouring nickel in the periodic table of elements, for their capacity to activate human monocyte-derived dendritic cells (MoDCs).. The panel included chromium, cobalt, and palladium, all of which are known to be frequent clinical sensitizers. MoDC activation was monitored by assessment of release of the pro-inflammatory mediator interleukin (IL)-8, a major downstream result of TLR ligation. Results The data obtained in the present study show that cobalt and palladium also have potent MoDC-activating capacities, whereas copper and zinc, but not iron and chromium, have low but distinct MoDC-activating potential. Involvement of endotoxin contamination in MoDC activation was excluded by Limulus assays and consistent stimulation in the presence of polymyxin B. The critical role of TLR4 in nickel-induced, cobalt-induced and palladium-induced activation was confirmed by essentially similar stimulatory patterns obtained in an HEK293 TLR4/MD2 transfectant cell line.. Given the adjuvant role of costimulatory danger signals, the development of contact allergies to the stimulatory metals may be facilitated by signals from direct TLR4 ligation, whereas other metal sensitizers, such as chromium, may rather depend on microbial or tissue-derived cofactors to induce clinical sensitization.

    Topics: Biomarkers; Cells, Cultured; Chromium; Cobalt; Dendritic Cells; Dermatitis, Allergic Contact; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-8; Nickel; Palladium; Toll-Like Receptor 4; Transition Elements

2013
The balance between pro- and anti-inflammatory cytokines is crucial in human allergic contact dermatitis pathogenesis: the role of IL-1 family members.
    Experimental dermatology, 2013, Volume: 22, Issue:12

    The interleukin (IL)-1 family includes 11 members that are important in inflammatory processes. It includes various agonists and two antagonists, IL-1Ra and IL-36Ra. Our aim was to investigate whether the IL-1 family is involved in allergic contact dermatitis (ACD). The expression of IL-1 family members was evaluated by PCR and immunohistochemistry in the positive patch test reaction site (involved skin) and in the uninvolved skin of ACD patients. We also examined these cytokines in an ex vivo model of ACD. The antagonistic activity of IL-36Ra was evaluated by injecting recombinant IL-36Ra in uninvolved skin biopsies of ACD patients. IL-1Ra and IL-36Ra expression was quantified in mononuclear cells of nickel-sensitized patients challenged in vitro with nickel. IL-33 involvement in ACD was investigated by intra-dermal injection of anti-IL-33 in the uninvolved skin of patients ex vivo. Results showed that IL-1β, IL-1Ra, IL-36α, IL-36β, IL-36γ and IL-33 expression, but not IL-36Ra expression, was enhanced in ACD-involved skin. Immunohistochemical analysis and ex vivo skin cultures confirmed these results. Injection of anti-IL-33 in ACD-uninvolved skin inhibited IL-8 expression, whereas IL-36Ra inhibited IL-36α, IL-36β, IL-36γ and IL-8 expression. Nickel induced IL-1Ra expression in lymphocytes of nickel-sensitized patients. Hence, various IL-1 agonists and antagonists may be involved in ACD pathogenesis.

    Topics: Adult; Biopsy; Cytokines; Dermatitis, Allergic Contact; Humans; Inflammation; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-33; Interleukin-8; Interleukins; Leukocytes, Mononuclear; Middle Aged; Recombinant Proteins; Skin

2013
Antiallergic effects of Scutellaria baicalensis on inflammation in vivo and in vitro.
    Journal of ethnopharmacology, 2012, May-07, Volume: 141, Issue:1

    Scutellaria baicalensis (SB) is one of the most widely used medicinal herbs for the treatment of inflammation. In this study, we investigated the antiallergic effect of SB in vivo and in vitro.. Sprague-Dawley (SD) rats received intradermal injections of anti-DNP IgE at each of three dorsal skin sites. Forty-eight hours later, each rat received an injection of DNP-HSA in saline containing 4% Evans blue through the dorsal vein of the penis. One hour before injection, SB extract was administered orally. The dorsal skin of the rats was removed and the pigment area measured. In addition, rat peritoneal mast cells (RPMCs) were cultured and purified to investigate histamine release. In vitro, human mast cells (HMC-1) were pretreated with SB extract for 30min before stimulation with phorbol 12-myristate 13-acetate (PMA) plus A23187. The effects on pro-inflammatory cytokine expression and mitogen activated protein (MAP) kinase expression were investigated using TNF-α and IL-8 assays, and Western blotting analysis of HMC-1 cells.. SB treatment inhibited the passive cutaneous anaphylaxis reaction compared to the control group, and histamine release decreased significantly following treatment of RPMCs with SB. In HMC-1 cells, SB restored IL-8 and TNF-α expression and inhibited MAP kinase expression in compound 48/80-induced HMC-1 cells. These data suggest that SB may prove to be a useful anti-inflammatory agent through its downregulation of the expression of various inflammatory mediators.

    Topics: Administration, Oral; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Blotting, Western; Calcimycin; Calcium Ionophores; Cells, Cultured; Dermatitis, Allergic Contact; Dinitrophenols; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Activation; Female; Haptens; Histamine Release; Humans; Inflammation Mediators; Interleukin-8; Mast Cells; Mitogen-Activated Protein Kinases; p-Methoxy-N-methylphenethylamine; Phytotherapy; Plant Extracts; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Scutellaria baicalensis; Serum Albumin; Tetradecanoylphorbol Acetate; Time Factors; Tumor Necrosis Factor-alpha

2012
Tacrolimus modulates dendritic cell activation in the sensitization phase of allergic contact dermatitis.
    Skin pharmacology and physiology, 2010, Volume: 23, Issue:1

    Knowledge of the effect of topically applied calcineurin antagonists such as tacrolimus on the sensitization phase of allergic contact dermatitis is currently limited.. To investigate tacrolimus-dependent immunomodulation on gene expression alterations in human antigen-presenting cells which are stimulated with small-molecular-weight contact allergens.. Monocyte-derived dendritic cells (moDC) and THP-1 cells were stimulated with the contact sensitizer cinnamic aldehyde (CAld) and compared with the very strong experimental sensitizer 2,4,6-trinitrobenzene sulfonic acid (TNBS) in vitro. Quantitative PCR analysis was used to detect gene expression changes, particularly of interleukin (IL) 8, as an indicator of differential dendritic cell (DC) gene expression after sensitizer stimulation in the absence or presence of tacrolimus and betamethasone at two different concentrations.. DC activation was clearly demonstrated by a significant IL-8 upregulation after 24 h, whereas tacrolimus or betamethasone alone did not affect IL-8 baseline expression. Betamethasone and, to a lesser extent, tacrolimus led to a marked reduction of chemical-induced IL-8 expression by TNBS and CAld.. The results of the present study support the hypothesis that the calcineurin inhibitor tacrolimus has modulatory effects on human antigen-presenting cells during the sensitization phase of allergic contact dermatitis. In addition, moDC as well as THP-1 cells may serve as a system to study immune-modulating effects of drugs such as glucocorticoids or calcineurin antagonists.

    Topics: Acrolein; Antigen-Presenting Cells; Betamethasone; Cell Line, Tumor; Dendritic Cells; Dermatitis, Allergic Contact; Gene Expression Regulation; Humans; Immunosuppressive Agents; Interleukin-8; Monocytes; Polymerase Chain Reaction; Tacrolimus; Trinitrobenzenesulfonic Acid

2010
Role of p38 MAPK in the selective release of IL-8 induced by chemical allergen in naive THp-1 cells.
    Toxicology in vitro : an international journal published in association with BIBRA, 2008, Volume: 22, Issue:2

    At present, the assessment of the allergenic potential of chemicals is carried out using animal models. Over the last decade, several in vitro methods mainly using primary dendritic cells have been proposed to identify the potential of chemicals to induce skin sensitization to meet current animal welfare and public opinions. The major limitations of such tests are the donor-to-donor variability, the low levels in the source, and a possible shortage of human sources. The aim of the present investigation was to establish an in vitro test to identify chemical allergens using the human promyelocytic cell line THP-1 in order to avoid some of these difficulties. We investigated whether the chemokine interleukin-8 or CXCL8 (IL-8) production could provide a methodology for the detection of both respiratory and contact allergens. THP-1 cells were exposed to contact allergens (cinnamaldehyde, dinitrochlorobenzene, nickel sulfate, penicillin G, p-phenylenediamine, tetramethylthiuram disulfide), to respiratory allergens (ammonium hexachloroplatinate, diphenylmethane diisocyanate, trimellitic anhydride) and to irritants (salicylic acid, phenol, sodium lauryl sulphate). Following 48 h of incubation, the release of IL-8 was evaluated by sandwich ELISA. IL-8 production was significantly increased after stimulation with all allergens tested, with the exception of trimellitic anhydride, whereas irritants exposure failed to induce IL-8 release. The lack of IL-8 production by trimellitic anhydride can be explained by the rapid hydrolysis of this chemical in water to trimellitic acid, which is not an allergen. In contrast to IL-8 release, CD54 and CD86 expression did not provide a sensitive method failing to correctly identify approximately 30% of the tested compounds. Although CD86 appears to be a more sensitive marker than CD54 when discriminating allergens from irritants neither of these markers provided robust methodology. We also investigated if a common activation pathway in allergen-induced IL-8 production involving p38 mitogen-activated protein kinase could be identified. By Western blot analysis we could indeed demonstrate p38 activation by all chemical allergens tested and, using the selective p38 MAPK inhibitor SB203580, a significant modulation of allergen-induced IL-8 release could be achieved in all cases. Our data suggests that production of IL-8 by naïve THP-1 cells may represent a promising in vitro model for the screening of potential chemical allergens and

    Topics: Allergens; Animal Testing Alternatives; Antigens, Surface; B7-2 Antigen; Cell Line; Data Interpretation, Statistical; Dendritic Cells; Dermatitis, Allergic Contact; Flow Cytometry; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Irritants; p38 Mitogen-Activated Protein Kinases; Stimulation, Chemical

2008
A skin-like cytochrome P450 cocktail activates prohaptens to contact allergenic metabolites.
    The Journal of investigative dermatology, 2007, Volume: 127, Issue:5

    Allergic contact dermatitis is a complex syndrome representing immunological responses to cutaneous exposure to protein-reactive chemicals. Although many contact sensitizers directly can elicit this disorder, others (prohaptens) require activation. Knowledge regarding the activating mechanisms remains limited, but one possibility is metabolic activation by cytochrome P450 (CYP) enzymes in the skin. We have, after quantitative reverse transcriptase-PCR studies of the CYP content in 18 human skin samples, developed an enriched skin-like recombinant human (rh) CYP cocktail using CYP1A1, 1B1, 2B6, 2E1, and 3A5. To validate the rhCYP cocktail, a prohaptenic conjugated diene ((5R)-5-isopropenyl-2-methyl-1-methylene-2-cyclohexene) was investigated using: the skin-like rhCYP cocktail, a liver-like rhCYP cocktail, single rhCYP enzymes, liver microsomes, keratinocytes, and a dendritic cell (DC) assay. The diene was activated to sensitizing epoxides in all non-cell-based incubations including the skin-like rhCYP cocktail. An exocyclic epoxide metabolite ((7R)-7-isopropenyl-4-methyl-1-oxaspiro[2.5]oct-4-ene) was found to be mainly responsible for the allergenic activity of the diene. This epoxide also induced pronounced DC activation indicated by upregulation of IL-8. The skin-like rhCYP cocktail provides a simplified alternative to using skin tissue preparations in mechanistic studies of CYP-mediated skin metabolism of prohaptens and offers the future possibility of designing in vitro predictive assays for assessment of allergenic activity of prohaptens.

    Topics: Allergens; Animals; Biotransformation; Cells, Cultured; Cytochrome P-450 Enzyme System; Dendritic Cells; Dermatitis, Allergic Contact; Female; Haptens; Humans; Interleukin-8; Keratinocytes; Male; Mice; Mice, Inbred Strains; Microsomes, Liver; RNA, Messenger; Skin; Up-Regulation

2007
Delayed and immediate allergy caused by methylhexahydrophthalic anhydride.
    Contact dermatitis, 1997, Volume: 36, Issue:1

    Epoxy resin compounds (ERC) include a large number of chemicals, such as epoxy resins (ER), reactive diluents and hardeners. Many hardeners, e.g., aliphatic polyamines, are well-known sensitizers. Another type of ER hardeners are the phthalic anhydrides, such as methylhexahydrophthalic anhydride (MHHPA) and methyltetrahydrophthalic anhydride (MTHPA), which have been reported as causing immunologically-mediated respiratory diseases and contact urticaria, but not allergic contact dermatitis. Here, we present a horizontal boring-machine worker who developed allergic contact dermatitis, as well as allergic rhinitis and an immediate contact skin reaction from MHHPA. Patch testing with a dilution series of MHHPA in pet. elicited the following results: 2%, 1% and 0.5%, +2; 0.25% and 0.125%, + (3- to 6-day readings). An immunohistochemical and electron microscopic study also indicated that the patch test reactions were conventional-delayed allergic reactions. Interleukin 8 was observed in the epidermal cells, whereas interleukin 4 immunoreactivity was detected in the dermal cells. Immunoreactivity to-interleukin 5, granulocyte/macrophage-colophony stimulating factor (GM-CSF) or eosinophil cationic protein was not seen. In conclusion, the patient developed both Type I and Type IV allergy to MHHPA. The clinical data, patch test results, immunohistochemical and electron microscopic observations indicated that the MHHPA allergy detected by the patch test reaction was a conventional delayed-type hypersensitivity reaction. The patient also had an allergic patch test reaction to para-phenylenediamine and diaminodiphenylmethane, possibly representing occupational sensitization.

    Topics: Allergens; Aniline Compounds; Blood Proteins; Dermatitis, Allergic Contact; Dermatitis, Occupational; Eosinophil Granule Proteins; Eosinophils; Epidermis; Epoxy Resins; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunohistochemistry; Inflammation Mediators; Interleukin-4; Interleukin-5; Interleukin-8; Male; Microscopy, Electron; Middle Aged; Patch Tests; Phenylenediamines; Phthalic Anhydrides; Respiratory Hypersensitivity; Rhinitis; Ribonucleases; Skin; Urticaria

1997