IL-1 receptor antagonist attenuates MAP kinase/AP-1 activation and MMP1 expression in UVA-irradiated human fibroblasts induced by culture medium from UVB-irradiated human skin keratinocytes.
Solar UV light comprises UVB wavelengths (290-320 nm) and UVA wavelengths (320-400 nm). UVB radiation reaches the epidermis and, to a lesser extent, the upper part of the dermis, while UVA radiation penetrates more deeply into human skin. Existing studies have demonstrated that UV-irradiated epidermal keratinocytes release cytokines that indirectly promote MMP-1 production in dermal fibroblasts. In this study, we first investigated the effect of IL-1 on MAPK activity, c-Jun and c-Fos mRNA expression, and MMP-1 and MMP-2 production in UVA-irradiated human dermal fibroblasts. The results showed that UVA irradiation dose-dependently increased MMP-1 but not MMP-2 production in human skin fibroblasts. IL-1alpha and IL-1beta promoted MMP-1 but not MMP-2 production in UVA-irradiated fibroblasts. Both IL-1alpha and IL-1beta activated MAP kinase, significantly elevating c-Jun and c-Fos mRNA expression. We then investigated the indirect effect of UVB-irradiated keratinocyte culture medium on MMP-1 production in UVA-irradiated primary cultured human dermal fibroblasts and the effect of IL-1Ra. The results showed that cell culture medium from UVB-irradiated keratinocytes increased MMP-1 production in UVA-irradiated fibroblasts, and IL-1Ra dose-dependently inhibited MMP-1 production. IL-1Ra dose-dependently inhibited c-Jun mRNA expression of fibroblasts with no significant effect on c-Fos mRNA expression. These results demonstrate that UVB-irradiated keratinocytes promoted MMP-1 production in UVA-irradiated fibroblasts in a paracrine manner while IL-1Ra reduced MMP-1 production through inhibiting c-Jun mRNA expression. Collectively, our data suggest that IL-1 plays an important role in the dermal collagen degradation associated with UV-induced premature aging of the skin and IL-1Ra may be applied for the prevention and treatment of photoaging.
Wang
Xiaoyong
X
Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, PR China.
Bi
Zhigang
Z
Chu
Wenming
W
Wan
Yinsheng
Y
D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects*; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000494:pharmacology*; D012867:Skin / Q000166:cytology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014466:Ultraviolet Rays
D017077:Culture Media, Conditioned; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1