Wound healing in the skin is accompanied by inflammation. Increasing evidence indicates that the proinflammatory cytokine interleukin 6 (IL-6), plays an important role in wound healing. However, the mechanisms of IL-6 production and involvement in wound healing remain unclear. The present study was designed to examine the molecular mechanism of IL-6 production, and its involvement in wound healing in normal human epidermal keratinocyre (NHEK) using an in vitro wounding model. Herein, we demonstrate that IL-6 mRNA expression and immunoreactive IL-6 release were increased following wounding. The transcription factors NF-KB and NF-IL6 (C/EBPB), which are known to be involved in IL-6 induction, were also activated following wounding. Addition of IL-1 increased IL-6 production and induced NF-KB and C/EBPB activation in NHEK. Exogenous IL-1 receptor antagonist inhibited IL-6 mRNA expression and transcription factor activation following wounding. Immunoreactive IL-1 was detected in the culture medium following wounding, but mRNA was not increased. Additionally, mRNA expression of keratins 1 and 10, which are differentiation markers of keratinocyres, was decreased in wounded NHEK or keratinocytes treated with exogenous IL-6. Thus, these data indicate that the primary stimulus for IL-6 production in wounded epidermis is aurocrine/paracrine stimulus with IL-l, and the mechanism by which IL-6 aids in wound healing is associated with the inhibition of differentiation in epidermal keratinocytes.
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California