Document Detail

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.
MedLine Citation:
PMID:  16273295     Owner:  NLM     Status:  MEDLINE    
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.
Xiaoyong Wang; Zhigang Bi; Wenming Chu; Yinsheng Wan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of molecular medicine     Volume:  16     ISSN:  1107-3756     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-07     Completed Date:  2006-02-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1117-24     Citation Subset:  IM    
Department of Dermatology, First Affiliated Hospital of Nanjing Medical University, Jiangsu Province, Nanjing 210029, PR China.
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MeSH Terms
Cells, Cultured
Culture Media, Conditioned / pharmacology*
Enzyme Activation / drug effects
Enzyme Induction / radiation effects
Fibroblasts / drug effects*,  enzymology,  metabolism,  radiation effects*
Gene Expression Regulation
Genes, fos / drug effects
Genes, jun / drug effects
Interleukin 1 Receptor Antagonist Protein
Interleukin-1 / pharmacology
Keratinocytes* / metabolism,  radiation effects
Matrix Metalloproteinase 1 / antagonists & inhibitors,  metabolism*
Matrix Metalloproteinase 2 / biosynthesis
Mitogen-Activated Protein Kinases / metabolism*
RNA, Messenger / genetics,  metabolism
Sialoglycoproteins / pharmacology*
Skin / cytology
Transcription Factor AP-1 / metabolism*
Ultraviolet Rays
Grant Support
Reg. No./Substance:
0/Culture Media, Conditioned; 0/IL1RN protein, human; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; 0/RNA, Messenger; 0/Sialoglycoproteins; 0/Transcription Factor AP-1; EC Protein Kinases; EC Metalloproteinase 2; EC Metalloproteinase 1

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