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Production of interleukin-1 receptor antagonist by human articular chondrocytes.

Abstract : Interleukin-1 receptor antagonist (IL-1Ra) is a natural IL-1 inhibitor possessing anti-inflammatory properties. IL-1Ra is produced as different isoforms, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, icIL-1Ra2 and icIL-1Ra3), derived from the same gene. We examined the production of IL-1Ra species by cultured human articular chondrocytes in response to various cytokines. The levels of IL-1Ra were undetectable in culture supernatants of untreated cells, but were significantly increased by IL-1beta. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1beta, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1beta, while dexamethasone prevented the response. We observed by RT-PCR that IL-1beta and IL-6 induced primarily the production of sIL-1Ra mRNA. Furthermore, IL-1beta alone or combined with IL-6 increased the levels of nascent unspliced sIL-1Ra mRNA, suggesting that sIL-1Ra expression is regulated at the transcriptional level. Reporter gene assays in immortalized chondrocytes, C-20/A4, consistently showed increased sIL-1Ra promoter activity in response to IL-1beta and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1beta and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses.
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Submitted on : Tuesday, January 16, 2007 - 11:28:24 AM
Last modification on : Friday, July 17, 2020 - 10:56:02 AM
Long-term archiving on: : Tuesday, April 6, 2010 - 8:13:25 PM

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  • HAL Id : inserm-00124790, version 1
  • PUBMED : 12010575

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Gaby Palmer, Pierre-André Guerne, Françoise Mezin, Michel Maret, Jérôme Guicheux, et al.. Production of interleukin-1 receptor antagonist by human articular chondrocytes.. Arthritis Research, BioMed Central, 2002, 4 (3), pp.226-31. ⟨inserm-00124790⟩

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