Open AccessInduction of α 1 ‐antitrypsin synthesis in human articular chondrocytes by interleukin‐6–type cytokines: Evidence for a local acute‐phase response in the joint
Author(s) -
Fischer DagmarChristiane,
Siebertz Barbara,
Van De Leur Eddy,
SchiwyBochat KarlHeinz,
Graeve Lutz,
Heinrich PeterC.,
Haubeck HansDieter
Publication year - 1999
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199909)42:9<1936::aid-anr20>3.0.co;2-k
Subject(s) - oncostatin m , proinflammatory cytokine , acute phase protein , interleukin , cartilage , arthritis , chondrocyte , immunology , chemistry , microbiology and biotechnology , inflammation , cytokine , interleukin 6 , medicine , biology , anatomy
Objective We have previously shown that human articular chondrocytes synthesize large amounts of interleukin‐6 (IL‐6) upon stimulation with proinflammatory cytokines and that they express the IL‐6 receptor. The present study was undertaken to analyze whether different IL‐6–type cytokines can induce synthesis of the acute‐phase protein α 1 ‐antitrypsin in human articular chondrocytes. Methods Chondrocytes from human articular cartilage, cultured in agarose, were stimulated with IL‐6–type cytokines. Total RNA was isolated and analyzed by Northern blotting. Levels of α 1 ‐antitrypsin protein were determined by enzyme immunoassay. Results Stimulation of chondrocytes with oncostatin M (OSM) and IL‐6 led to a 5–10‐fold increase in α 1 ‐antitrypsin synthesis. This increase was dose and time dependent. Furthermore, OSM and IL‐6 induced IL‐6 synthesis in chondrocytes, resulting in an autocrine amplification loop. Conclusion Our data strongly suggest the existence of a local acute‐phase response in the joint. Synthesis of the acute‐phase protein α 1 ‐antitrypsin, a major inhibitor of serine proteinases, may be an important protective mechanism of articular chondrocytes to prevent cartilage damage in inflammatory joint diseases.