Effects of IL-36 cytokines on S100A7/psoriasin and cathelicidin LL-37 expression and production by primary human keratinocytes

IL-36 is the common name for the three IL-1 family members IL-36α, IL-36β, and IL-36γ, formerly known as IL-1F6, IL-1F8, and IL-1F9, respectively. IL-36 has recently been detected in keratinocytes, and is involved in skin diseases such as psoriasis, where host defense peptides S100A7/psoriasin and LL-37 are highly expressed. However; the effects of IL-36 on psoriasin and LL-37 production by keratinocytes remain largely unknown. The aim of this study is to investigate the effects of IL-36 cytokines on S100A7/psoriasin and LL-37 expression and production by keratinocytes, and to elucidate the possible mechanisms underlying this production. The ability of IL-36 cytokines to induce mRNA expression and protein production of S100A7/psoriasin and LL-37 by keratinocytes was determined by real-time PCR and ELISA, respectively. Phosphorylation of MAPKs and IκB-α was determined by Western blotting. We found that all of the three IL-36 cytokines enhanced S100A7/psoriasin and LL-37 gene expression and protein production by keratinocytes in dose-dependent manner; however, IL-36β and IL-36γ were more active than IL-36α. Furthermore, IL-36s stimulated phosphorylation of MARKs ERK, p38 and JNK and IκB-α. The induction of S100A7/psoriasin and LL-37 production by IL-36 cytokines involved ERK, p38, JNK and NF-κB, as evidenced by the specific inhibitory effects of U0126, SB203580, JNK inhibitor II and NF-κB activation inhibitor II, respectively. In conclusion, the finding that IL-36 cytokines stimulate the production of psoriasin and LL-37 by keratinocytes provides novel mechanism by which these cytokines contribute the pathogenesis of psoriasis and innate immunity through stimulation of host defense peptides S100A7/psoriasin and LL-37. JSID AbstractsJournal of Dermatological ScienceVol. 69Issue 2Preview Full-Text PDF