Induction of alpha1-antitrypsin synthesis in human articular chondrocytes by interleukin-6-type cytokines: evidence for a local acute-phase response in the joint.
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 alpha1-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 alpha1-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 alpha1-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.


CONCLUSIONS
Our data strongly suggest the existence of a local acute-phase response in the joint. Synthesis of the acute-phase protein alpha1-antitrypsin, a major inhibitor of serine proteinases, may be an important protective mechanism of articular chondrocytes to prevent cartilage damage in inflammatory joint diseases.
Fischer
D C
DC
Universitätsklinikum der Rheinische-Westfälische Technische Hochschule Aachen, Germany.
Siebertz
B
B
van de Leur
E
E
Schiwy-Bochat
K H
KH
Graeve
L
L
Heinrich
P C
PC
Haubeck
H D
HD
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000494:pharmacology; D015152:Blotting, Northern; D019902:Chondrocytes / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D007596:Joints / Q000378:metabolism; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000096:biosynthesis*
D000209:Acute-Phase Proteins; D000970:Antineoplastic Agents; D016207:Cytokines; D006131:Growth Inhibitors; D018836:Inflammation Mediators; D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin; D053683:Oncostatin M