Selenomethionine inhibits IL-1ß inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes.

OBJECTIVE: Several lines of evidence show that selenium (Se) has potential protective effects in osteoarthritis (OA), however the exact mechanism is still unclear. As interleukin-1ß (IL-1ß) is one of the key proinflammatory cytokines contributing to the progression in OA, we investigated the effect of Se in neutralizing the inflammatory effects of IL-1ß on nitric oxide (NO) and prostaglandin E2 (PGE2) production, and the signaling pathways involved. METHODS: Isolated primary human chondrocytes were pretreated with selenomethionine (SeMet) (0.5 µM SeMet) for 24 h then co-treated without or with IL-1ß (10 pg/ml or 50 pg/ml) for another 24 h followed by RNA isolation. Gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) was determined by quantitative Real Time-Polymerase Chain Reaction. Culture media concentrations of NO and PGE2 were determined by nitrite (NO2⁻) assay and immunoassay respectively. For analysis of cell signaling pathways, chondrocytes were pretreated with SeMet then stimulated with IL-1ß for 0-45 min. The activity of IL-1ß signaling pathways was determined by Western blot screening of phosphorylation states of signal transduction proteins. RESULTS: SeMet inhibited chondrocyte gene expression of IL-1ß induced iNOS (31-54%, P=0.031) and COX2 (50-65%, P=0.031) with corresponding reductions in both NO (19-47%, P=0.031) and PGE2 (24-32%, P=0.031) production. Pretreatment with SeMet attenuated IL-1ß induced activation of p38 MAPK (39%, P=0.039) but not the extracellular signal-regulated kinase pathways (ERK) 1/2, c-Jun N-terminal kinases (JNK) or nuclear factor κB (NFκB). CONCLUSIONS: This study elucidates one potential protective mechanism of Se, namely through the alteration of cell signaling and downstream transcription of pro-inflammatory effects of IL-1ß.