Autoinhibition of IL-15 expression in KC cells is ERK1/2 and PI3K dependent.

Interleukin (IL)-15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL-15 on expression of IL-15, IL-6 and TNF-alpha in KC are unknown. We have investigated the effects of IL-15 on the expression of the three genes in primary culture of KC by the real-time PCR, Western blot and ELISA. We observed that exogenous IL-15 suppressed the endogenous expression of IL-15, decreased the expression of IL-6 at mRNA and protein levels in KC. The inhibition was blocked by anti-IL-15 monoclonal antibody and by inactive IL-15, I50D mutant IL-15. In contrast, IL-15 increased TNF-alpha transcription in these cells. Mechanistic studies demonstrated that the auto-regulation of IL-15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto-inhibitory mechanism controlling cellular IL-15 levels.