Interleukin-1beta and macrophage migration inhibitory factor (MIF) in dermal fibroblasts mediate UVA-induced matrix metalloproteinase-1 expression.
BACKGROUND
Exposure to solar UV radiation is the main environmental factor that causes premature aging of the skin. Matrix metalloproteinases (MMP)-1 is a member of the MMP family and degrades types I and III collagens, which are the major structural components of the dermis.


OBJECTIVE
We evaluated the involvement IL-1beta and macrophage migration inhibitory factor (MIF) in MMP-1 expression under ultraviolet A (UVA) irradiation.


METHODS
IL-1beta and MIF in MMP-1 expression in cultured human dermal fibroblasts and the UVA effects on MMPs production using IL-1alpha/beta-deficient mice were analyzed. Furthermore, fibroblasts derived from MIF-deficient mice were used to analyze the effect of IL-1beta-induced MMPs production.


RESULTS
IL-1beta-enhanced MIF expression and induced MMP-1 in cultured human dermal fibroblasts. IL-1beta-induced MMP-1 expression is inhibited by neutralizing anti-MIF antibody. Dermal fibroblasts of IL-1alpha/beta-deficient mice produced significantly decreased levels of MMPs compared to wild-type mice after UVA irradiation. Furthermore, fibroblasts of MIF-deficient mice were much less sensitive to IL-1beta-induced MMPs production. On the contrary, IL-1beta produced significantly decreased levels of MMPs in MIF-deficient mice fibroblasts. The up-regulation of MMP-1 mRNA by IL-1beta stimulation was found to be inhibited by a p38 inhibitor and a JNK inhibitor. In contrast, the MEK inhibitor and inhibitor were found to have little effect on expression of MMP-1 mRNA.


CONCLUSIONS
IL-1beta is involved in the up-regulation of UVA-induced MMP-1 in dermal fibroblasts, and IL-1beta and MIF cytokine network induce MMP-1 and contribute to the loss of interstitial collagen in skin photoaging.
Department of Dermatology, Graduate School of Medicine, University of Toyama, Toyama, Japan.
Ayumi
A
Honda
Riichiro
R
Abe
Teruhiko
T
Makino
Osamu
O
Norisugi
Yasuyuki
Y
Fujita
Hirokazu
H
Watanabe
Jun
J
Nishihira
Yoichiro
Y
Iwakura
Sho-ichi
S
Yamagishi
Hiroshi
H
Shimizu
Tadamichi
T
Shimizu
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics* / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000378:metabolism; D015595:Skin Aging / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D000906:Antibodies; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C076231:Mif protein, mouse