Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-κB inactivation

Kyung Min Shin, Liulan Shen, Seung Jae Park, Jin Hyun Jeong, Kyung Tae Lee

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Objectives: Previously, we reported that diaryl diselenide compounds have strong inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophages. In this study, we investigated the molecular mechanisms underlying NO suppression and prostaglandin E2 (PGE 2) production by diaryl diselenide compounds, bis-(2-hydroxyphenyl) diselenide (DSE-A), bis-(3-hydroxyphenyl) diselenide (DSE-B), bis-(4-hydroxyphenyl) diselenide (DSE-C), dipyridyl diselenide (DSE-D) and diphenyl diselenide (DSE-E). Methods: The effect of these compounds on NO suppression and PGE2 production was investigated in RAW 264.7 macrophages. Key findings: Our data indicate that of the above, DSE-B most potently inhibits NO and PGE2 production, and that it also significantly reduces the releases of tumour necrosis factor (TNF)-α, interleukin(IL)-1β and IL-6. Consistent with these observations, DSE-B also reduced the protein levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), and the mRNA levels of iNOS, COX-2, TNF-α, IL-1β and IL-6. Furthermore, DSE-B inhibited LPS-induced nuclear factor-κB (NF-κB) activation, which was associated with the prevention of the inhibitor κB-α (IκB-α) degradation and a subsequent reduction in nuclear p65 protein levels. Conclusions: Taken together, our data suggest that the anti-inflammatory properties of DSE-B are due to reduction in the expression of iNOS, COX-2, TNF-α, IL-1β and IL-6 through the down-regulation of NF-κB binding activity.

Original languageEnglish
Pages (from-to)479-486
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume61
Issue number4
DOIs
Publication statusPublished - 2009 Apr 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this