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

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Cyclooxygenase 2
Nitric Oxide Synthase
Lipopolysaccharides
Nitric Oxide
Macrophages
Interleukin-1
Dinoprostone
Interleukin-6
Tumor Necrosis Factor-alpha
Nitric Oxide Synthase Type II
Nuclear Proteins
Anti-Inflammatory Agents
Down-Regulation
Messenger RNA
RAW 264.7 Cells
bis(3-hydroxyphenyl) diselenide
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

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title = "Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-κB inactivation",
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.",
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Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-κB inactivation. / Shin, Kyung Min; Shen, Liulan; Park, Seung Jae; Jeong, Jin Hyun; Lee, Kyung Tae.

In: Journal of Pharmacy and Pharmacology, Vol. 61, No. 4, 01.04.2009, p. 479-486.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-κB inactivation

AU - Shin, Kyung Min

AU - Shen, Liulan

AU - Park, Seung Jae

AU - Jeong, Jin Hyun

AU - Lee, Kyung Tae

PY - 2009/4/1

Y1 - 2009/4/1

N2 - 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.

AB - 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.

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