title: Interleukin-10 does not affect IL-1-induced interleukin-6 and metalloproteinase production in human chondrosarcoma cells, SW1353.
abstract: Cartilage repair by transplantation of autologous chondrocytes is an option when restoring functional joints. Control of chondrocyte function is thus required. Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine affecting the expression of a wide range of immune mediators in hematopoietic and non-hematopoietic cells. Previous studies indicated that IL-10 has therapeutic potential in the treatment of chronic inflammatory joint disorders such as rheumatoid arthritis and osteoarthritis. IL-10 has been found to be chondroprotective by down-regulating metalloproteinase expression and by inhibiting the synthesis of pro-inflammatory cytokines, such as IL-6, in immune cells. In contrast, the effects of IL-10 on chondrocytes are poorly understood and have to be identified with regard to their future clinical use. In this study, we investigated the effects of IL-10 on the expression of cartilage-degrading mediators in the human chondrosarcoma cell line, SW1353, after exposure to IL-1, a key mediator in cartilage and bone destruction. We found a strong induction of the pro-inflammatory cytokine, IL-6, in IL-1-exposed SW1353 cells. Surprisingly, IL-10 had no effect on IL-1-induced IL-6, pro-MMP1, and pro-MMP13 secretion. Although RT-PCR analyses demonstrated the expression of both receptor chains of the IL-10 receptor complex (IL-10R1 and IL-10R2), exposure of SW1353 to IL-10 did not lead to phosphorylation of STAT3, the major transcription factor induced by IL-10. This was not due to a defect in STAT3, because stimulation with IL-6 resulted in its phosphorylation. Failure of SW1353 cells to respond to IL-10 was consistent with a deficient surface expression of IL-10R1. From these results we conclude that IL-10 does not exert its chondroprotective character on chondrocytes directly. Furthermore, the unresponsiveness of chondrocytes towards IL-10 might explain the vulnerability of joint cartilage to inflammation.
authors.affiliation: Abteilung Hämatologie und Internistische Onkologie, Universität Regensburg, D-93053 Regensburg, Germany. juergen.radons@klinik.uni-regensburg.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Radons
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Thomas E O
authors.initials: TE
authors.lastname: Schubert
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000145:classification / Q000235:genetics / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D045726:Metalloproteases / Q000096:biosynthesis*; D051379:Mice; D018123:Receptors, Interleukin / Q000378:metabolism; D053701:Receptors, Interleukin-10; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D045726:Metalloproteases