Methotrexate normalized keratinocyte activation cycle by overturning abnormal keratins as well as deregulated inflammatory mediators in psoriatic patients

Abstract

Background: In psoriatic skin, epidermal keratinocytes undergo deregulated inflammatory response that leads to prolonged expression of inflammatory mediators as well as abnormal keratins. Methotrexate (MTX) is an immunosuppressive agent used as a standard drug to treat severe psoriasis. The aim of the study is to find the pharmacological effect of MTX on abnormal keratin and deregulated inflammatory mediators.

Methods: Fifty-eight psoriasis vulgaris patients were recruited for this study. Skin biopsies of psoriatic patients were collected and analyzed for activation signal such as TNF-α and IFN-γ and deactivation signal such as TGF-β1. Also, protein and gene expression of normal keratins K14 and K10 and abnormal keratins K16 and K17 were analyzed in skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment.

Results: Results show a significant decrease in tissue TNF-α and IFN-γ and increase in TGF-β1 after MTX treatment when compared with before MTX treatment in psoriasis patients (p<0.001). Protein and gene expression of K14, K16 and K17 decreased after MTX treatment, whereas the expression of differentiation marker K10 increased after MTX treatment.

Conclusion: MTX resolves deregulated inflammatory markers and maintains normal keratin phenotype on hyperproliferating KC, thereby controlling acanthosis in psoriasis patients.

Keywords: Interferon-γ; Keratin 16; Keratin 17; Methotrexate; Transforming growth factor-β(1).