The role of IL-4 and IL-6 in IL-1-dependent cartilage matrix degradation.
The objective of this paper was to study the effects of interleukin 4 (IL-4) and interleukin 6 (IL-6) on cartilage matrix degradation, the production of chondroitin-4-sulphate (C4S) and chondroitin-6-sulphate (C6S), metalloproteinase (stromelysin 1 = MMP-3) and metalloproteinase inhibitor (TIMP-1) production. Cartilage matrix degradation was assayed the release of 35SO4 from chondrocyte cultures. TIMP-1 and MMP-3 were measured by ELISA. C6S and C4S were measured by HPLC analysis. IL-1 beta significantly enhanced C4S production and significantly suppressed C6S production. Thus, the C4S/C6S ratio was significantly enhanced by IL-1 beta, and significantly suppressed by IL-4. IL-4 removed the suppressing effects of IL-1 beta for C6S and the enhancing effects of IL-1 beta for the C4S/C6S ratio. Whereas IL-1 beta stimulated the production of MMP-3, IL-4 and IL-6 had no effect on enzyme activity. IL-4, but not IL-6, removed the enhancing effects of IL-1 beta for MMP-3. In contrast, IL-4 and IL-6 significantly enhanced TIMP-1 production in chondrocytes, IL-4, but not IL-6, also significantly suppressed IL-1 beta-mediated cartilage matrix degradation. On the other hand, IL-6 significantly suppressed spontaneous cartilage matrix degradation which is supposed to be mediated by the autocrine IL-1 mechanisms. In conclusion our results suggest that IL-4 and IL-6 both protect the cartilage matrix degradation induced by IL-1.
Shingu
M
M
Department of Clinical Immunology, Kyushu University, Beppu, Japan.
Miyauchi
S
S
Nagai
Y
Y
Yasutake
C
C
Horie
K
K
D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis; D013431:Sulfates / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases
D016207:Cytokines; D006023:Glycoproteins; D007375:Interleukin-1; D015850:Interleukin-6; D013431:Sulfates; D019714:Tissue Inhibitor of Metalloproteinases; D015847:Interleukin-4; D002809:Chondroitin Sulfates; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3