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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-kappaB inactivation.
J Pharm Pharmacol. 2009 Apr; 61(4):479-86.JP

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 E(2) (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 PGE(2) production was investigated in RAW 264.7 macrophages.

KEY FINDINGS

Our data indicate that of the above, DSE-B most potently inhibits NO and PGE(2) production, and that it also significantly reduces the releases of tumour necrosis factor (TNF)-alpha, interleukin(IL)-1beta 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-alpha, IL-1beta and IL-6. Furthermore, DSE-B inhibited LPS-induced nuclear factor-kappaB (NF-kappaB) activation, which was associated with the prevention of the inhibitor kappaB-alpha (IkappaB-alpha) 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-alpha, IL-1beta and IL-6 through the down-regulation of NF-kappaB binding activity.

Authors+Show Affiliations

College of Pharmacy, Kyung-Hee University, Dongdaemun-gu, Seoul, South Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19298695

Citation

Shin, Kyung-Min, et al. "Bis-(3-hydroxyphenyl) Diselenide Inhibits LPS-stimulated iNOS and COX-2 Expression in RAW 264.7 Macrophage Cells Through the NF-kappaB Inactivation." The Journal of Pharmacy and Pharmacology, vol. 61, no. 4, 2009, pp. 479-86.
Shin KM, Shen L, Park SJ, et al. Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-kappaB inactivation. J Pharm Pharmacol. 2009;61(4):479-86.
Shin, K. M., Shen, L., Park, S. J., Jeong, J. H., & Lee, K. T. (2009). Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-kappaB inactivation. The Journal of Pharmacy and Pharmacology, 61(4), 479-86. https://doi.org/10.1211/jpp/61.04.0010
Shin KM, et al. Bis-(3-hydroxyphenyl) Diselenide Inhibits LPS-stimulated iNOS and COX-2 Expression in RAW 264.7 Macrophage Cells Through the NF-kappaB Inactivation. J Pharm Pharmacol. 2009;61(4):479-86. PubMed PMID: 19298695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bis-(3-hydroxyphenyl) diselenide inhibits LPS-stimulated iNOS and COX-2 expression in RAW 264.7 macrophage cells through the NF-kappaB inactivation. AU - Shin,Kyung-Min, AU - Shen,Liulan, AU - Park,Seung Jae, AU - Jeong,Jin-Hyun, AU - Lee,Kyung-Tae, PY - 2009/3/21/entrez PY - 2009/3/21/pubmed PY - 2009/6/9/medline SP - 479 EP - 86 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 61 IS - 4 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 E(2) (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 PGE(2) production was investigated in RAW 264.7 macrophages. KEY FINDINGS: Our data indicate that of the above, DSE-B most potently inhibits NO and PGE(2) production, and that it also significantly reduces the releases of tumour necrosis factor (TNF)-alpha, interleukin(IL)-1beta 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-alpha, IL-1beta and IL-6. Furthermore, DSE-B inhibited LPS-induced nuclear factor-kappaB (NF-kappaB) activation, which was associated with the prevention of the inhibitor kappaB-alpha (IkappaB-alpha) 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-alpha, IL-1beta and IL-6 through the down-regulation of NF-kappaB binding activity. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/19298695/Bis__3_hydroxyphenyl__diselenide_inhibits_LPS_stimulated_iNOS_and_COX_2_expression_in_RAW_264_7_macrophage_cells_through_the_NF_kappaB_inactivation_ L2 - https://doi.org/10.1211/jpp/61.04.0010 DB - PRIME DP - Unbound Medicine ER -