Ethanol-Modulated Cytokine Production and Expression in Skin Cells Exposed to Methotrexate
| Autor: | Marina Landau, Gady G. Katz, Neil H. Shear, Manuela G. Neuman, Izabella M. Malkiewicz |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Chemokine Physiology medicine.medical_treatment Dermatology Cell Line Proinflammatory cytokine Internal medicine medicine Humans Drug Interactions Viability assay skin and connective tissue diseases Skin Pharmacology Ethanol biology Tumor Necrosis Factor-alpha business.industry Infant Newborn Antibodies Monoclonal Interleukin General Medicine Glutathione Methotrexate Endocrinology Cytokine Apoptosis Toxicity biology.protein Cytokines RNA Tumor necrosis factor alpha business |
| Zdroj: | Skin Pharmacology and Physiology. 12:64-78 |
| ISSN: | 1660-5535 1660-5527 |
| Popis: | Evidence suggests a link between alcohol consumption, psoriasis and the response of psoriatic patients to methotrexate (MTX) therapy. Ethanol (EtOH) may play a role in the pathogenesis of psoriasis by upregulating the expression and inducing the local secretion of proinflammatory cytokines, e.g. interleukins IL-1α, IL-6, chemokine IL-8 and tumor necrosis factor alpha (TNF-α). We investigated whether EtOH or MTX or their combination influence the secretion of these cytokines using normal human primary skin cells (NHPSC) and epidermoid cell line A431. The objectives of this study were: (1) to quantify the differences in cellular changes induced by MTX, (2) to measure the effect of EtOH on MTX toxicity and (3) to determine the relationship between MTX and EtOH exposure and production of proinflammatory cytokines. NHPSC and A431 were incubated with 0–10 mM MTX or α-MEM (control) in the presence or absence of 40 mM EtOH. A formazan 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used as a marker for cell viability (control was 100%). Significance was calculated by ANOVA. Cytokine release into media was quantitated by ELISA. After 24 h of MTX exposure, the release of IL-1α was unchanged. IL-6 increased 1.7 times in both cultures, and IL-8 increased 1.7 times in NHPSC and 2.1 times in A431. TNF-α release increased twice in A431 but not in NHPSC. Human recombinant IL-1α and IL-6 for 24 h had no effect, while TNF-α reduced cytoviability by 30% in NHPSC and 22% in A431. Anti-TNF-α reversed the effect produced by TNF-α in NHPSC and reduced it in A431 (11.8%, p < 0.05). We concluded that in vitro in normal human primary keratinocytes, toxicity and inflammatory responses are enhanced by EtOH. |
| Databáze: | OpenAIRE |
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