%0 Journal Article
%T Artesunate Exerts a Direct Effect on Endothelial Cell Activation and NF- B Translocation in a Mechanism Independent of Plasmodium Killing
%A Mariana C. Souza
%A Fl¨¢vio Henrique Marcolino Paix£¿o
%A Fausto K. Ferraris
%A Isabela Ribeiro
%A Maria das Gra£¿as M. O. Henriques
%J Malaria Research and Treatment
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/679090
%X Artemisinin and its derivates are an important class of antimalarial drug and are described to possess immunomodulatory activities. Few studies have addressed the effect of artesunate in the murine malaria model or its effect on host immune response during malaria infection. Herein, we study the effect of artesunate treatment and describe an auxiliary mechanism of artesunate in modulating the inflammatory response during experimental malaria infection in mice. Treatment with artesunate did not reduce significantly the parasitemia within 12£¿h, however, reduced BBB breakdown and TNF-¦Á mRNA expression in the brain tissue of artesunate-treated mice. Conversely, mefloquine treatment was not able to alter clinical features. Notably, artesunate pretreatment failed to modulate the expression of LFA-1 in splenocytes stimulated with parasitized red blood cells (pRBCs) in vitro; however, it abrogated the expression of ICAM-1 in pRBC-stimulated endothelial cells. Accordingly, a cytoadherence in vitro assay demonstrated that pRBCs did not adhere to artesunate-treated vascular endothelial cells. In addition, NF-¦ÊB nuclear translocation in endothelial cells stimulated with pRBCs was impaired by artesunate treatment. Our results suggest that artesunate is able to exert a protective effect against the P. berghei-induced inflammatory response by inhibiting NF-¦ÊB nuclear translocation and the subsequent expression of ICAM-1. 1. Introduction Artesunate is a semisynthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua which has been used as a remedy for fevers and chills for centuries in China [1]. Artemisinin and its derivatives are the most important class of antimalarial drug effective for both uncomplicated and severe malaria [2]. Besides, artemisinin and its derivates have been shown to possess anticancer [3], antiviral [4], and anti-inflammatory [5¨C8] activities. Artesunate has been reported to block the production of IL-1 , IL-6 and IL-8 from TNF- -stimulated human rheumatoid arthritis fibroblast-like synoviocytes [9]. In addition, artesunate inhibits expression of toll-like receptor 4 induced by heat-killed E. coli lipopolysaccharide and production of TNF- , IL-6, and nitric oxide (NO). Further studies also demonstrated that artesunate protects septic mice challenged with S. aureus inhibiting TLR2 and Nod2 expression, and, consequently, decreasing TNF- release [10] probably regulating the transcription factor F-¦ÊB activation. There are also some evidences that artesunate attenuates experimental allergic airway
%U http://www.hindawi.com/journals/mrt/2012/679090/