Showing papers by "Gaby Palmer published in 2002"

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-1β. Cell lysates contained very low levels of IL-1Ra, even in response to IL-1β, suggesting that chondrocytes produce predominantly sIL-1Ra. IL-6, which had no effect on its own, enhanced the effect of IL-1β, while dexamethasone prevented the response. We observed by RT-PCR that IL-1β and IL-6 induced primarily the production of sIL-1Ra mRNA. Furthermore, IL-1β 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-1β and IL-6. In conclusion, human articular chondrocytes produce sIL-1Ra in response to IL-1β and IL-6. The production of sIL-1Ra by chondrocytes may have a protective effect against articular inflammatory and catabolic responses.

Primary human articular chondrocytes, dedifferentiated chondrocytes, and synoviocytes exhibit differential responsiveness to interleukin-4: correlation with the expression pattern of the common receptor gamma chain.

Abstract: Interleukin (IL)-4, which exhibits potent anti-inflammatory activities, is of potential therapeutic value in destructive arthropathies To further define the response of human joint cells to IL-4, we analyzed the ability of this cytokine to modulate the effects of IL-1beta and growth factors Freshly isolated chondrocytes, dedifferentiated chondrocytes, and synoviocytes were treated with IL-4 before determination of nitric oxide (NO) and collagenase production in response to IL-1beta, or before proliferation assays in presence of IL-1beta, platelet-derived growth factor (PDGF), or transforming growth factor (TGF)-beta IL-4 downregulated IL-1beta induced NO production in dedifferentiated chondrocytes and inhibited IL-1beta induced collagenase release, as well as IL-1beta and growth factor induced proliferation in dedifferentiated chondrocytes and synoviocytes In contrast, IL-4 had no effect in freshly isolated primary chondrocytes and in cartilage explants The lack of response to IL-4 in primary chondrocytes was associated with impaired signal transduction, as indicated by markedly decreased IL-4 dependent tyrosine phosphorylation of signal transducer and activator of transcription (STAT)-6 It also correlated with differences in the expression pattern of IL-4 receptor (IL-4R) subunits during chondrocyte dedifferentiation Indeed, whereas the IL-4Ralpha and IL-13Ralpha' subunits were expressed in all cell types, expression of the common receptor gamma chain was restricted to freshly isolated chondrocytes In conclusion, IL-4 downregulated IL-1beta-induced catabolic events and cell proliferation in dedifferentiated chondrocytes and synoviocytes, but had no effects in freshly isolated chondrocytes The difference in IL-4 responsiveness between primary and dedifferentiated chondrocytes correlated with changes in proximal signaling events and in the expression pattern of IL-4R subunits during cell dedifferentiation