UVA-induced autocrine stimulation of fibroblast-derived collagenase/MMP-1 by interrelated loops of interleukin-1 and interleukin-6.
Previous work has shown that fibroblast-derived collagenase/matrix-metalloproteinase-1 (MMP-1), responsible for the breakdown of dermal interstitial collagen, was dose-dependently induced in vitro and in vivo by UVA irradiation and this induction was at least partly mediated by interleukin-6 (IL-6). We here provide evidence that UVA-induced IL-1 alpha and IL-1 beta play a central role in the induction of the synthesis both of IL-6 and collagenase/MMP-1. In contrast to the late increase of IL-1 alpha and IL-1 beta mRNA levels at 6 h postirradiation, bioactivity of IL-1 is already detectable at 1 h postirradiation. This early peak of IL-1 bioactivity appears to be responsible for the induction of IL-6 synthesis and together with IL-6 lead to an increase of the steady-state mRNA level of collagenase/MMP-1 as deduced from studies using IL-1 alpha and IL-1 beta antisense oligonucleotides or neutralizing antibodies against IL-1 alpha and IL-1 beta. Besides the early posttranslationally controlled release of intracellular IL-1, a latter pretranslationally controlled synthesis and release of IL-1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting of IL-1 alpha, IL-1 beta and IL-6, which via interrelated autocrine loops induce collagenase/MMP-1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging.
Wlaschek
M
M
Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Germany.
Heinen
G
G
Poswig
A
A
Schwarz
A
A
Krieg
T
T
Scharffetter-Kochanek
K
K
D000375:Aging / Q000528:radiation effects; D017364:Collagenases / Q000096:biosynthesis / Q000528:radiation effects; D004790:Enzyme Induction / Q000528:radiation effects; D005347:Fibroblasts / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000528:radiation effects; D015850:Interleukin-6 / Q000096:biosynthesis / Q000528:radiation effects; D008297:Male; D020781:Matrix Metalloproteinase 1; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017364:Collagenases; D020781:Matrix Metalloproteinase 1