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J Biol Chem, Vol. 273, Issue 22, 13625-13629, May 29, 1998
From the Divisions of To define the potential role of interleukin-6
(IL-6) and its soluble receptor
Interleukin (IL)-6 and Its Soluble Receptor Induce TIMP-1
Expression in Synoviocytes and Chondrocytes, and Block IL-1-induced
Collagenolytic Activity
,,
Rheumatology,
§ Immunology and Allergy, and ¶ Orthopedic Surgery,
Hôpital Cantonal Universitaire,
1211 Geneva 14, Switzerland
in cartilage metabolism, we
analyzed their effects on tissue inhibitor of metalloproteases (TIMP)
synthesis by synoviocytes and chondrocytes. TIMP-1 production by
isolated human articular synovial fibroblasts and chondrocytes,
stimulated by IL-6 and/or its soluble receptor, was first assayed by
specific enzyme-linked immunosorbent assay; the slight stimulatory
effect of IL-6 on TIMP-1 production by both types of cells was markedly amplified by the addition of soluble receptor, the maximal secretion being observed only at 96 h. TIMP-1 mRNA expression,
determined by ribonuclease protection assay, was induced by IL-6
together with its soluble receptor, but TIMP-2 and -3 mRNAs were
not affected by these factors. A specific neutralizing antibody
abolished the effects of the soluble receptor. Finally, supernatant
from synoviocytes stimulated by IL-6 plus its soluble receptor blocked
almost completely the collagenolytic activity of supernatant from
IL-1-induced synoviocytes. These observations indicate that IL-6 and
its soluble receptor have a protective role in the metabolism of
cartilage. Given the high levels of soluble receptor in synovial fluid
and the marked induction of IL-6 by IL-1 or TNF-, it is likely that
IL-6 and its soluble receptor are critical in controlling the catabolic effects of pro-inflammatory cytokines.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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