Regulation of nitric oxide and prostaglandin E2 production by CSAIDS (SB203580) in murine macrophages and bovine chondrocytes stimulated with LPS.
OBJECTIVE
To compare two anti-inflammatory drugs: CSAIDS (SB203580) and hydrocortisone on iNOS and COX-2 expression.


METHODS
Murine macrophages and bovine chondrocytes stimulated with LPS and human OA-affected cartilage were used in this study.


METHODS
The macrophages and chondrocytes were preincubated (30 min) with 0.1-1.0 microM CSAIDS or 10 microM of hydrocortisone before stimulating them with 1-100 microg/ml LPS.


METHODS
The end products of iNOS and COX-2: nitric oxide (NO) and PGE2 were estimated by Greiss method and RIA, respectively.


RESULTS
CSAIDS (1 microM) inhibited the production of NO and PGE2 (p< or =0.01) in bovine chondrocytes, but not in murine macrophages (RAW 264.7) (p< or =0.1). In fact, CSAIDS (in murine macrophages) marginally augmented nitrite accumulation (approximately 20%) at 14-24 h of LPS stimulation. Western blot analysis of COX-2 in bovine chondrocytes show decrease in COX-2 expression by hydrocortisone but not CSAIDS, although hydrocortisone and CSAIDS inhibit PGE2 accumulation. Hydrocortisone inhibited both PGE2 and NO production significantly (p< or =0.01) in murine macrophages. Furthermore, hydrocortisone significantly inhibited (p< or =0.01) PGE2 but marginally (p< or =0.05) NO in bovine chondrocytes.


CONCLUSIONS
These experiments demonstrate differential action of CSAIDS and hydrocortisone on NO and PGE2 production in bovine chondrocytes and RAW 264.7 cells.
Patel
R
R
Department of Rheumatology, Hospital for Joint Diseases, New York, NY 10003, USA.
Attur
M G
MG
Dave
M N
MN
Kumar
S
S
Lee
J C
JC
Abramson
S B
SB
Amin
A R
AR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011725:Pyridines; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C093642:SB 203580; D006854:Hydrocortisone