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


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.

SUBMITTER: Cheng AW 

PROVIDER: S-EPMC3053078 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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

Cheng A W M AW   Stabler T V TV   Bolognesi M M   Kraus V B VB  

Osteoarthritis and cartilage 20101028 1


<h4>Objective</h4>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.<h4>Methods</h4>Isolated primary human c  ...[more]

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