Open Access

IL-33 regulates TNF-α dependent effects in synovial fibroblasts

  • Authors:
    • Elke Kunisch
    • Saritha Chakilam
    • Muktheshwar Gandesiri
    • Raimund W. Kinne
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  • Published online on: January 10, 2012     https://doi.org/10.3892/ijmm.2012.883
  • Pages: 530-540
  • Copyright: © Kunisch et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The recently described IL-33 acts as a pro-inflammatory 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-α 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-α significantly induced IL-33 mRNA expression and protein synthesis in RA-SFs. TNF-α-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-α stimulated RA-SFs. IL-33 overexpression enhanced TNF-α-induced pro-inflammatory and pro-destructive functions in RA-SFs. IL-33 silencing significantly downregulated TNF-α-induced pro-inflammatory functions, whereas TNF-α-induced pro-destructive functions were less influenced by IL-33 silencing. This study identifies IL-33 as a critical regulator/enhancer of TNF-α-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.
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April 2012
Volume 29 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kunisch E, Chakilam S, Gandesiri M and Kinne RW: IL-33 regulates TNF-α dependent effects in synovial fibroblasts . Int J Mol Med 29: 530-540, 2012
APA
Kunisch, E., Chakilam, S., Gandesiri, M., & Kinne, R.W. (2012). IL-33 regulates TNF-α dependent effects in synovial fibroblasts . International Journal of Molecular Medicine, 29, 530-540. https://doi.org/10.3892/ijmm.2012.883
MLA
Kunisch, E., Chakilam, S., Gandesiri, M., Kinne, R. W."IL-33 regulates TNF-α dependent effects in synovial fibroblasts ". International Journal of Molecular Medicine 29.4 (2012): 530-540.
Chicago
Kunisch, E., Chakilam, S., Gandesiri, M., Kinne, R. W."IL-33 regulates TNF-α dependent effects in synovial fibroblasts ". International Journal of Molecular Medicine 29, no. 4 (2012): 530-540. https://doi.org/10.3892/ijmm.2012.883