Myeloid differentiation factor 88 regulates basal and UV-induced expressions of IL-6 and MMP-1 in human epidermal keratinocytes.
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 (MyD88DeltaC), and dominant-negative (MyD88DeltaN) MyD88 forms. Overexpression of MyD88wt and MyD88DeltaC, but not of MyD88DeltaN, increased the basal expressions of IL-6 and matrix metalloproteinase-1 (MMP-1) in human epidermal keratinocytes. Moreover, overexpression of MyD88DeltaN prevented UV-induced expressions of IL-6 and MMP-1 by inhibiting UV-induced activation of NF-kappaB 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.
Lee
Youngae
Y
Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
Kim
Hyunjung
H
Kim
Sangmin
S
Shin
Mi Hee
MH
Kim
Yeon Kyung
YK
Kim
Kyu Han
KH
Chung
Jin Ho
JH
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D016296:Mutagenesis / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015595:Skin Aging / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects
D015850:Interleukin-6; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D020781:Matrix Metalloproteinase 1