Effects of interleukin-6 on the metabolism of connective tissue components in rheumatoid synovial fibroblasts.
OBJECTIVE
High levels of interleukin-6 (IL-6) have been found in the synovial fluid of patients with rheumatoid arthritis (RA). We undertook the present study to investigate the role of IL-6 in this disease.


METHODS
We examined the effects of IL-6, in comparison with IL-1, on the biosynthesis of extracellular matrix macromolecules and of matrix-degrading proteinases in rheumatoid synovial fibroblasts.


RESULTS
In rheumatoid synovial fibroblasts, IL-6 by itself enhanced the production of plasminogen activator, its inhibitor, and tissue inhibitor of metalloproteinases, whereas it did not modulate the biosynthesis of precursor of matrix metalloproteinase 1 (proMMP-1) (tissue collagenase), proMMP-3 (stromelysin), or connective tissue components. However, IL-1-induced production of proMMP-1 and proMMP-3 was preferentially augmented by IL-6.


CONCLUSIONS
These results suggest that in RA, IL-6 may participate along with IL-1 in fine tuning of the catabolism of connective tissue components, by modulating the balance between connective tissue-degrading enzymes and their inhibitors.
Ito
A
A
Department of Biochemistry, Tokyo College of Pharmacy, Japan.
Itoh
Y
Y
Sasaguri
Y
Y
Morimatsu
M
M
Mori
Y
Y
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis; D003238:Connective Tissue / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000096:biosynthesis; D006025:Glycosaminoglycans / Q000096:biosynthesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D013583:Synovial Membrane / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D006023:Glycoproteins; D006025:Glycosaminoglycans; D007375:Interleukin-1; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D019714:Tissue Inhibitor of Metalloproteinases; D003094:Collagen; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases