Myeloid Differentiation Factor 88 Regulates Basal and UV-Induced Expressions of IL-6 and MMP-1 in Human Epidermal Keratinocytes

Abstract

Myeloid differentiation factor 88 (MyD88) is known as an adaptor protein for the Toll-like receptor (TLR) family and participates in signal transduction by binding to the cytoplasmic Toll/IL-1 receptor (TIR) domains of activated TLR. In this study, we demonstrated that expression of MyD88 is increased in photoaged skin compared with intrinsic aged human skin of the same elderly individuals, and that acute UV irradiation increases MyD88 expression in human skin in vivo. To investigate the effects of these high levels of MyD88 in photoaged skin and acutely UV-irradiated skin, human epidermal keratinocytes were infected with adenovirus expressing wild-type (MyD88wt), dominant-positive (MyD88 Delta C), and dominant-negative (MyD88 Delta N) MyD88 forms. Overexpression of MyD88wt and MyD88 Delta C, but not of MyD88 Delta N, increased the basal expressions of IL-6 and matrix metalloproteinase-1 (MMP-1) in human epidermal keratinocytes. Moreover, overexpression of MyD88 Delta N prevented UV-induced expressions of IL-6 and MMP-1 by inhibiting UV-induced activation of NF-kappa B and activating protein-1. These results suggest that MyD88 is important in IL-6 and MMP-1 expressions in both acutely UV-irradiated skin and in chronically sun-exposed human skin.