Ultraviolet-B induction of interstitial collagenase and stromelyin-1 occurs in human dermal fibroblasts via an autocrine interleukin-6-dependent loop.
Ultraviolet-B irradiation of human dermal fibroblasts has earlier been shown to induce matrix-degrading metalloproteinases, thus driving connective tissue degradation in photoaging and photocarcinogenesis. Herein, we report that Ultraviolet-B irradiation led to a dramatic increase in specific mRNA and protein levels of interstitial collagenase, stromelysin and interleukin-6. By contrast, the major tissue inhibitor of matrix-degrading metalloproteinases, TIMP-1, was unaffected. Monospecific neutralizing antibodies directed against human interleukin-6 significantly reduced the interstitial collagenase and stromelysin-1 protein levels. Taken together, our data provide the first evidence that Ultraviolet-B induction of interstitial collagenase and stromelysin-1 occurs via the synthesis and release of interleukin-6. Hence, this newly identified autocrine mechanism may contribute to dermal photodamage.
Brenneisen
P
P
Department of Dermatology, University of Cologne, Germany.
Wlaschek
M
M
Wenk
J
J
Blaudschun
R
R
Hinrichs
R
R
Dissemond
J
J
Krieg
T
T
Scharffetter-Kochanek
K
K
D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D017364:Collagenases / Q000378:metabolism*; D004790:Enzyme Induction; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D009500:Neutralization Tests; D014466:Ultraviolet Rays
D015850:Interleukin-6; D017364:Collagenases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1