Anti-inflammatory effects of dimemorfan on inflammatory cells and LPS-induced endotoxin shock in mice

CCUR > College of Kinesiology and Health > Department of Chinese Martial Arts > journal articles > Item 987654321/2623

Please use this identifier to cite or link to this item: https://irlib.pccu.edu.tw/handle/987654321/2623

Title:	Anti-inflammatory effects of dimemorfan on inflammatory cells and LPS-induced endotoxin shock in mice
Authors:	Wang, Y.H. Shen, Y.C. Liao, J.F. Li, C.H. Chou, C.Y. Liou, K.T. Chou, Y.C.
Contributors:	國術系
Keywords:	cytokine dimemorfan endotoxin shock iNOS microglial cells neutrophils NF-kappa B NO ROS
Date:	2008
Issue Date:	2009-11-09 16:08:00 (UTC+8)
Abstract:	Background and purpose: Dimemorfan (a sigma(1) receptor agonist) showed neuroprotective properties in animal models of inflammation-mediated neurodegenerative conditions, but its effects on inflammatory cells and systemic inflammation remain unclear. Experimental approach: The effects of dimemorfan on phorbol-12-myristate-13-acetate (PMA)- and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced neutrophils and lipopolysaccharide (LPS)-activated microglial cells, as well as LPSinduced endotoxin shock in mice were elucidated. Key results: Dimemorfan decreased PMA- and fMLP-induced production of reactive oxygen species (ROS) and CD11b expression in neutrophils, through mechanisms independent of s1 receptors, possibly by blocking ROS production and G-protein-mediated intracellular calcium increase. Dimemorfan also inhibited LPS-induced ROS and nitric oxide (NO) production, as well as that of monocyte chemoattractant protein-1 and tumour necrosis factor-alpha (TNF-alpha), by inhibition of NADPH oxidase (NOX) activity and suppression of iNOS up-regulation through interfering with nuclear factor kappa-B (NF-kappa B) signalling in microglial cells. Treatment in vivo with dimemorfan (1 and 5 mg kg(-1), i.p., at three successive times after LPS) decreased plasma TNF-alpha, and neutrophil infiltration and oxidative stress in the lung and liver. Conclusions and implications: Our results suggest that dimemorfan acts via s1 receptor-independent mechanisms to modulate intracellular calcium increase, NOX activity, and NF-kappa B signalling, resulting in inhibition of iNOS expression and NO production, and production of pro-inflammatory cytokines. These effects may contribute its anti-inflammatory action and protective effects against endotoxin shock in mice.
Relation:	BRITISH JOURNAL OF PHARMACOLOGY Volume: 154 Issue: 6 Pages: 1327-1338
Appears in Collections:	[Department of Chinese Martial Arts] journal articles

Files in This Item:

There are no files associated with this item.

Loading...