anthrax lethal toxin impairs il-8 expression in epithelial cells through inhibition of histone h3 modification炭疽致命的毒素会损害引发的表达在上皮细胞通过抑制组蛋白h3修改.pdfVIP

Anthrax Lethal Toxin Impairs IL-8 Expression in Epithelial Cells through Inhibition of Histone H3 Modification 1,2 3 1,2 1,2 1,2 Benoit Raymond , Eric Batsche , Florence Boutillon , Yong-Zheng Wu , Dominique Leduc , Viviane 1,2 ¨ 1,2 3 4,5 1,2 Balloy , Eloıse Raoust , Christian Muchardt , Pierre L. Goossens , Lhousseine Touqui * ´ ´ ´ ´ ´ ´ ´ ´ 1 Institut Pasteur, Unite de Defense Innee et Inflammation, Paris, France, 2 Unite Inserm, U.874, Paris, France, 3 Institut Pasteur, Unite de Regulation Epigenetique, Paris, ´ ´ ´ France, 4 Institut Pasteur, Unite des Toxines et Pathogenie Bacterienne, Paris, France, 5 CNRS, URA-2172, Paris, France Abstract Lethal toxin (LT) is a critical virulence factor of Bacillus anthracis, the etiological agent of anthrax, whose pulmonary form is fatal in the absence of treatment. Inflammatory response is a key process of host defense against invading pathogens. We report here that intranasal instillation of a B. anthracis strain bearing inactive LT stimulates cytokine production and polymorphonuclear (PMN) neutrophils recruitment in lungs. These responses are repressed by a prior instillation of an LT preparation. In contrast, instillation of a B. anthracis strain expressing active LT represses lung inflammation. The inhibitory effects of LT on cytokine product