Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases.
This study on the regulation of interleukin (IL)-11 expression in human connective tissue cells shows that IL-11 expression is not restricted to cells of hematopoietic origin but can also be induced in articular chondrocytes and synoviocytes. IL-11 mRNA was induced in chondrocytes in response to transforming growth factor (TGF)-beta 1 and IL-1 beta. Stimulation with IL-6 or growth factors, such as basic fibroblast growth factor, leukemia inhibitory factor, and platelet-derived growth factor-AA, had only weak or no detectable effects. Activation of protein kinase C by phorbol esters and inhibition of protein synthesis by cyclohexamide increased IL-11 transcripts, whereas calcium ionophore A23817 or dibutyryl cyclic AMP had no effect. Immunoprecipitations revealed the synthesis of IL-11 protein in response to TGF-beta 1, IL-1 beta, as well as phorbol 12-myristate 13-acetate, and a synergistic action of TGF-beta 1 and IL-1 beta was observed. Similar findings on IL-11 expression were made in synoviocytes. Analysis of effects on cell function showed that IL-11 stimulated the production of the tissue inhibitor of metalloproteinases in chondrocytes and synoviocytes but did not affect chondrocyte proliferation or increase stromelysin activity. These results suggest that IL-11 does not contribute to connective tissue degradation but conversely induces protective effects in joint tissue.
Maier
R
R
Sam and Rose Stein Institute for Research on Aging, Department of Medicine, University of California-San Diego, La Jolla 92093-0663.
Ganu
V
V
Lotz
M
M
D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D017370:Interleukin-11 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D006023:Glycoproteins; D007375:Interleukin-1; D017370:Interleukin-11; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta