Pacific ciguatoxin 1B-induced modulation of inflammatory mediators in a murine macrophage cell line

Abstract

Pacific ciguatoxin 1B-induced modulation of inflammatory mediators in a murine macrophage cell line Mariko Matsui a,b,c, Shilpa Kumar-Roine a,b,c, H. Taiana Darius d, Mireille Chinain d, Dominique Laurent b,c, Serge Pauillac a,* a Laboratoire des Biotoxines, Institut Pasteur de Nouvelle-Cale´donie, 9-11 Avenue Paul Doumer, BP61, 98845 Noumea, New Caledonia b Universite´ de Toulouse, UPS, UMR 152 (Laboratoire de pharmacochimie des substances naturelles et pharmacophores redox), 118, rte de Narbonne, F-31062 Toulouse cedex 9, France c IRD, UMR-152, BPA5, 98848 Noumea, New Caledonia d Laboratoire des Microalgues Toxiques, Institut Louis Malarde´, BP30, 98713 Papeete, Tahiti, French Polynesia a r t i c l e i n f o Article history: Received 27 March 2009 Received in revised form 14 May 2009 Accepted 14 May 2009 Available online xxxx Keywords: Ciguatera Fish Poisoning Cytokines Nitric oxide Neurotoxins Inflammatory system Quantitative PCR a b s t r a c t Ciguatoxins, potent marine neurotoxins responsible for ciguatera, exert their numerous damaging effects through primary binding to the voltage-sensitive sodium channels of excitable cells. Using RAW 264.7 murine macrophages, we report the first experimental study presenting evidence that P-CTX-1B (the most potent congener from the Pacific) could modulate mRNA expression of pro- and anti-inflammatory cytokines as well as of inducible nitric oxide synthase (iNOS). P-CTX-1B, unlike other less potent marine polyether toxins, P-CTX-3C and PbTx-3, induced the overexpression of interleukin (IL)-1b, IL-6, IL-10, tumor necrosis factor-a and iNOS with different magnitude and kinetic profiles, as compared to bacterial lipopolysaccharide (LPS). Unlike LPS, P-CTX-1B did not modulate IL- 11 expression. In this report, we provide new evidence of the P-CTX-1B iNOS- and cyto- kines-inducing ability and shed new light on host response to potent neurotoxins.  2009 Elsevier Ltd. All rights reserved. 1. Introduction Among the worldwide existing sea

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