UVA-INDUCED AUTOCRINE STIMULATION OF FIBROBLAST-DERIVED COLLAGENASE/MMP-1 BY INTERRELATED LOOPS OFINTERLEUKIN–1 andINTERLEUKIN–6 |
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Authors: | Meinhard Wlaschek Gudrun Heinen Arndt Poswig Agatha Schwarz Thomas Krieg Karin Scharffetter-Kochanek |
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Institution: | Department of Dermatology, Heinrich-Heine-University of Düsseldorf, Dusseldorf, Germany;Department of Dermatology, LBI-DVS, Laboratory for Cell Biology, University of Minister, Minister, Germany;Department of Dermatology, University of Cologne, Joseph-Stelzmannstr. 9, 50931 Cologne, Germany |
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Abstract: | Abstract— 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 byinterleukin–6(IL–6). We here provide evidence that UVA-inducedIL–1α andIL–1β play a central role in the induction of the synthesis both ofIL–6 and collagenase/MMP–1. In contrast to the late increase ofIL–1α andIL–1β mRNA levels at 6 h postirradiation, bioactivity ofIL–1 is already detectable at 1 h postirradiation. This early peak ofIL–1 bioactivity appears to be responsible for the induction ofIL–6 synthesis and together withIL–6 lead to an increase of the steady-state mRNA level of collagenase/MMP–1 as deduced from studies usingIL–1α andIL–1β antisense oligonucleotides or neutralizing antibodies againstIL–1α andIL–1β Besides the early posttranslationally controlled release of intracellularIL–1, a latter pretranslationally controlled synthesis and release ofIL–1 perpetuates the UV response. From these data we suggest a UV-induced cytokine network consisting ofIL–1α,IL–1β andIL–6, which via interrelated autocrine loops induce collagenase/MMP–1 and thus may contribute to the loss of interstitial collagen in cutaneous photoaging. |
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