UVA-induced autocrine stimulation of fibroblast-derived-collagenase by IL-6: a possible mechanism in dermal photodamage?
Like other cytokines, IL-6 has been reported to stimulate collagenase. In this study we were interested in whether IL-6 is involved in the ultraviolet (UV) mediated up-regulation of fibroblast-derived collagenase. Confluent fibroblast monolayers were irradiated under standardized conditions. Following UVA irradiation the bioactivity of IL-6 increased up to fiftyfold in the supernatants of irradiated compared to mock-irradiated fibroblasts. As determined by Northern blot analysis this was also reflected on the pre-translational level by a tenfold increase of IL-6-specific mRNA following UVA irradiation. Induction of IL-6-specific mRNA was maximal at 6 h post-irradiation, thus clearly preceding the maximal induction of collagenase mRNA at 24 h post-irradiation. To elucidate the regulatory role of IL-6 in the UVA induction of fibroblast-derived collagenase, monospecific polyclonal neutralizing antibodies directed against recombinant human IL-6 and antisense oligonucleotides specifically inhibiting the translation of IL-6 mRNA were used at various concentrations. The amount of UVA-induced collagenase mRNA was reduced in a dose-dependent manner when antibodies or specific antisense oligonucleotides were present during and after irradiation. Taken together our data provide first evidence that UVA enhances IL-6 synthesis and secretion in fibroblasts. IL-6 induces via an autocrine mechanism collagenase and may thus contribute to the actinic damage of the dermis.
Wlaschek
M
M
Department of Dermatology, University of Düsseldorf, F.R.G.
Bolsen
K
K
Herrmann
G
G
Schwarz
A
A
Wilmroth
F
F
Heinrich
P C
PC
Goerz
G
G
Scharffetter-Kochanek
K
K
D000185:Actinin / Q000494:pharmacology; D000906:Antibodies; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000235:genetics / Q000528:radiation effects; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D009500:Neutralization Tests; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D013194:Staining and Labeling; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects; D014841:von Willebrand Factor / Q000276:immunology
D000906:Antibodies; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014841:von Willebrand Factor; D000185:Actinin; D017364:Collagenases