IL-17A Upregulates Keratin 17 Expression in Keratinocytes through STAT1- and STAT3-Dependent Mechanisms

Abstract

Psoriasis, an immunological skin disease, is characterized by epidermal hyperproliferation, chronic inflammation, and an accumulation of infiltrating T cells. IL-17A is a key cytokine that has a critical role in the pathogenesis of psoriasis. Keratin 17 (K17) is strongly expressed in psoriatic lesions but not in normal skin. Thus, K17 expression is regarded as a hallmark of psoriasis. We previously reported that the K17/T cells/cytokine autoimmune loop was involved in psoriasis. However, the relationship between IL-17A and K17 has yet to be determined. In the present study, IL-17A-induced K17 expression was confirmed in cultured keratinocytes in both mRNA and protein levels. In addition, increased K17 expression was found in the epidermis of IL-17A-injected mouse skin. The regulatory mechanism of K17 expression was further investigated. We found that both the signal transducer and activator of transcription (STAT) 1 and STAT3 pathways were involved in the upregulation of K17 expression induced by IL-17A, and that such regulation could be partially suppressed by STAT1 or STAT3 small interfering RNA and inhibitor. Our data suggest that IL-17A can upregulate K17 expression in keratinocytes in a dose-dependent manner through STAT1- and STAT3-dependent mechanisms. The results indicate that IL-17A might be an important cytokine in the K17/T cells/cytokine autoimmune loop associated with psoriasis.