Selective iNOS inhibitor 1400W enhances anti-catabolic IL-10 and reduces destructive MMP-10 in OA cartilage. Survey of the effects of 1400W on inflammatory mediators produced by OA cartilage as detected by protein antibody array.
OBJECTIVE
In osteoarthritis (OA), the balance between catabolic and anabolic mediators and their regulators in cartilage is disturbed. Proinflammatory cytokine interleukin-1 (IL-1) plays a central role in cartilage destruction and nitric oxide (NO) mediates many of its destructive effects. In the present study, we investigated the secretion of 40 mediators related to inflammation or cartilage degradation by OA cartilage samples with a protein antibody array. The effects of IL-1 and a selective iNOS-inhibitor 1400W on the mediator release were also studied.


METHODS
Cartilage tissue was obtained from the leftover pieces of total knee replacement surgery from OA patients. Protein antibody array was used to measure production of 40 mediators in the culture medium. ELISA was used to confirm the antibody array results.


RESULTS
OA cartilage secreted spontaneously 15 out of the 40 measured mediators. IL-1Beta enhanced production of 11 of these inflammatory mediators in OA cartilage along with increased NO production. Treatment with a selective iNOS inhibitor 1400W enhanced the production of IL-10, while the levels of MMP-10 were reduced in IL-1 -treated OA cartilage.


CONCLUSIONS
OA cartilage produces many of the mediators involved in the pathogenesis of OA. The ability of 1400W to enhance levels of anti-catabolic IL-10 and to reduce levels of destructive MMP-10 points to the anti-inflammatory mechanisms that iNOS-inhibitors may have.
The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland.
K
K
Järvinen
K
K
Vuolteenaho
R
R
Nieminen
T
T
Moilanen
R G
RG
Knowles
E
E
Moilanen
D000328:Adult; D000578:Amidines / Q000494:pharmacology*; D000906:Antibodies; D001596:Benzylamines / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism*; D053506:Matrix Metalloproteinase 10 / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D040081:Protein Array Analysis
D000578:Amidines; D000906:Antibodies; D001596:Benzylamines; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D007375:Interleukin-1; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D016753:Interleukin-10; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D053506:Matrix Metalloproteinase 10