Publications [#188631] of Virginia B Kraus

Papers Published

1. AW Cheng, TV Stabler, M Bolognesi, VB Kraus, Selenomethionine inhibits IL-1β inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes., Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, vol. 19 no. 1 (January, 2011), pp. 118-25, ISSN 1522-9653 [doi]
   (last updated on 2011/03/23)

   Abstract:
   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-1β (IL-1β) 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-1β 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-1β (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-1β for 0-45 min. The activity of IL-1β signaling pathways was determined by Western blot screening of phosphorylation states of signal transduction proteins. RESULTS: SeMet inhibited chondrocyte gene expression of IL-1β 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-1β 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-1β.

   Keywords:
   Aged • Blotting, Western • Cells, Cultured • Chondrocytes • Cyclooxygenase 2 • Dinoprostone • Humans • Interleukin-1beta • Middle Aged • Nitric Oxide Synthase • RNA, Messenger • Selenomethionine • antagonists & inhibitors* • drug effects • drug effects* • metabolism • metabolism* • pharmacology*