title: PPARγ Agonists as an Anti-Inflammatory Treatment Inhibiting Rotavirus Infection of Small Intestinal Villi.
abstract: Rotavirus infection has been reported to induce an inflammatory response in the host cell accompanied by the increased expression or activation of some cellular molecules including ROS, NF-κB, and COX-2. PPARγ stimulation and N-acetylcysteine (NAC) treatment have been found to interfere with viral infections including rotavirus infection. Small intestinal villi isolated from in vivo infected mice with rotavirus ECwt were analyzed for the percentage of ECwt-infected cells, the presence of rotavirus antigens, and infectious virion yield following treatment with pioglitazone. Isolated villi were also infected in vitro and treated with PPARγ agonists (PGZ, TZD, RGZ, DHA, and ALA), all-trans retinoic acid (ATRA), and NAC. After treatments, the expression of cellular proteins including PPARγ, NF-κB, PDI, Hsc70, and COX-2 was analyzed using immunochemistry, ELISA, immunofluorescence, and Western blotting. The results showed that rotavirus infection led to an increased accumulation of the cellular proteins studied and ROS. The virus infection-induced accumulation of the cellular proteins studied and ROS was reduced upon pioglitazone treatment, causing also a concomitant reduction of the infectious virion yield. We hypothesized that rotavirus infection is benefiting from the induction of a host cell proinflammatory response and that the interference of the inflammatory pathways involved leads to decreased infection.
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Distrito Capital, Colombia.
authors.forename: Dory
authors.initials: D
authors.lastname: Gómez
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Distrito Capital, Colombia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Muñoz
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Distrito Capital, Colombia.
authors.forename: Rafael
authors.initials: R
authors.lastname: Guerrero
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Distrito Capital, Colombia.
authors.forename: Orlando
authors.initials: O
authors.lastname: Acosta
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Distrito Capital, Colombia.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guerrero