TGFbeta inhibits IL-1 -induced iNOS expression and NO production in immortalized chondrocytes.
OBJECTIVE
The balance between anti-inflammatory (e.g. TGFbeta) and proinflammatory cytokines (e.g. IL-1 and TNFalpha), regulates destructive processes in OA cartilage. IL-1 and TNFalpha enhance nitric oxide (NO) production in OA cartilage through the inducible nitric oxide synthase (iNOS) pathway and NO mediates many of the destructive effects of these cytokines. The aim of the present study was to investigate the effects of TGFbeta on NO production in immortalized H4 chondrocytes exposed to IL-1.


RESULTS
IL-1 induced NO production in chondrocytes through nuclear factor kappa B (NF-kappaB) sensitive and dexamethasone insensitive expression of iNOS. TGFbeta inhibited IL-1 -induced iNOS expression and NO production in chondrocytes, but it did not have any effect on iNOS mRNA levels. iNOS protein levels were similar in cells treated with IL-1 or IL-1+TGFbeta when measured after 8 h incubation, whereas when measured after 12 h and 24 h incubations, iNOS protein levels were 50% and 80% lower in cells treated with IL-1+TGFbeta than in cells treated with IL-1 alone.


CONCLUSIONS
TGFbeta suppressed IL-1-induced iNOS expression and NO production in chondrocytes, probably by enhancing iNOS protein degradation. This finding suggests an additional mechanism for TGFbeta to counteract the destructive effects of IL-1 in OA.
Vuolteenaho
K
K
The Immunopharmacological Research Group Medical School, University of Tampere and Research Unit, Tampere University Hospital, 33014 Tampere, Finland.
Moilanen
T
T
Jalonen
U
U
Lahti
A
A
Nieminen
R
R
van Beuningen
H M
HM
van der Kraan
P M
PM
Moilanen
E
E
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007375:Interleukin-1; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases