Wavelength-specific synergy between ultraviolet radiation and interleukin-1 alpha in the regulation of matrix-related genes: mechanistic role for tumor necrosis factor-alpha.
Ultraviolet light causes both acute and chronic changes in extracellular matrix. We sought to examine the effects of different ultraviolet wavelengths on expression of matrix-related genes in fibroblasts. We previously reported that tropoelastin gene expression in vivo decreases with acute ultraviolet B exposure, and interleukin-1 alpha-mediated upregulation of tropoelastin is blocked in vitro after ultraviolet B radiation. In this study, we found that only ultraviolet B, but not ultraviolet A or ultraviolet A1, blocked the ability of interleukin-1 alpha to stimulate tropoelastin expression in vitro. Ultraviolet B and interleukin-1 alpha synergistically increased tumor necrosis factor-alpha secretion by fibroblasts, a finding not seen with ultraviolet B alone nor with ultraviolet A or ultraviolet A1 combined with interleukin-1 alpha. Keratinocytes showed a similar ultraviolet B-specific induction of tumor necrosis factor-alpha production. Addition of tumor necrosis factor-alpha to cultured fibroblasts blocked interleukin-1 alpha-induced stimulation of tropoelastin message, and addition of anti-tumor necrosis factor-alpha antibodies restored the responsiveness of tropoelastin and collagen messages to exogenous interleukin-1 alpha after ultraviolet B exposure. We conclude that interleukin-1 alpha in combination specifically with ultraviolet B induces fibroblasts to secrete tumor necrosis factor-alpha, and that this ultraviolet B-specific induction of tumor necrosis factor-alpha secretion is responsible for effects of ultraviolet B on the expression of matrix-related genes in the skin.
Werth
V P
VP
Department of Dermatology, University of Pennsylvania, Philadelphia 19104, USA. werth@mail.med.upenn.edu
Zhang
W
W
D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism; D014333:Tropoelastin / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D007375:Interleukin-1; D014333:Tropoelastin; D014409:Tumor Necrosis Factor-alpha