Journal
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 29, Issue 4, Pages 530-540Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2012.883
Keywords
fibroblasts; interleukin-33; TNF-alpha; inflammatory diseases
Categories
Funding
- German Federal Ministry of Education and Research (BMBF) [FKZ 01ZZ9602, 01ZZ0105, 010405]
- Interdisciplinary Center for Clinical Research (IZKF) Jena [FKZ0312704B, 0313652B]
- Jena Centre for Bioinformatics [01GS0413, NGFN-2]
- German Research Foundation (DFG) [KI 439/7-1, KI 439/6-1]
Ask authors/readers for more resources
The recently described IL-33 acts as a proinflammatory cytokine, inducing the expression of multiple responses in the target cells. Although a nuclear localization of IL-33 has been described, its exact functional relevance is presently unknown. The present study was conducted to analyze the effects of IL-33 on the TNF-alpha induced synthesis of the pro-inflammatory mediators IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) and the pro-destructive molecules matrix metalloproteinase-1 (MMP-1), MMP-3, and TIMP-1 of rheumatoid arthritis synovial fibroblast (RA-SFs) using RNA overexpression and silencing. TNF-a significantly induced IL-33 mRNA expression and protein synthesis in RA-SFs. TNF-alpha-induced IL-33 protein expression was mediated via p38 signaling. Immunohistochemistry for IL-33 clearly showed that nuclear translocation of IL-33 was induced in TNF-alpha stimulated RA-SFs. IL-33 overexpression enhanced TNF-alpha-induced pro-inflammatory and pro-destructive functions in RA-SFs. IL-33 silencing significantly downregulated TNF-alpha-induced pro-inflammatory functions, whereas TNF-alpha-induced pro-destructive functions were less influenced by IL-33 silencing. This study identifies IL-33 as a critical regulator/enhancer of TNF-alpha-induced functions in RA-SFs, pointing to a central role of this cytokine in the perpetuation of pro-inflammatory and pro-destructive processes in rheumatoid arthritis (RA) and other inflammatory and degenerative diseases.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available