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dc.contributorVirginia Techen_US
dc.contributor.authorViladomiu, Monicaen_US
dc.contributor.authorHontecillas, Raquelen_US
dc.contributor.authorPedragosa, Mireiaen_US
dc.contributor.authorCarbo, Adriaen_US
dc.contributor.authorHoops, Stefanen_US
dc.contributor.authorMichalak, Pawelen_US
dc.contributor.authorMichalak, Katarzynaen_US
dc.contributor.authorGuerrant, Richard L.en_US
dc.contributor.authorRoche, James K.en_US
dc.contributor.authorWarren, Cirle A.en_US
dc.contributor.authorBassaganya-Riera, Josepen_US
dc.date.accessioned2014-06-17T20:12:08Z
dc.date.available2014-06-17T20:12:08Z
dc.date.issued2012-10-11en_US
dc.identifier.citationViladomiu M, Hontecillas R, Pedragosa M, Carbo A, Hoops S, et al. (2012) Modeling the Role of Peroxisome Proliferator-Activated Receptor γ and MicroRNA-146 in Mucosal Immune Responses to Clostridium difficile. PLoS ONE 7(10): e47525.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10919/48999
dc.description.abstractClostridium difficile is an anaerobic bacterium that has re-emerged as a facultative pathogen and can cause nosocomial diarrhea, colitis or even death. Peroxisome proliferator-activated receptor (PPAR) c has been implicated in the prevention of inflammation in autoimmune and infectious diseases; however, its role in the immunoregulatory mechanisms modulating host responses to C. difficile and its toxins remains largely unknown. To characterize the role of PPARc in C. difficileassociated disease (CDAD), immunity and gut pathology, we used a mouse model of C. difficile infection in wild-type and T cell-specific PPARc null mice. The loss of PPARc in T cells increased disease activity and colonic inflammatory lesions following C. difficile infection. Colonic expression of IL-17 was upregulated and IL-10 downregulated in colons of T cellspecific PPARc null mice. Also, both the loss of PPARc in T cells and C. difficile infection favored Th17 responses in spleen and colonic lamina propria of mice with CDAD. MicroRNA (miRNA)-sequencing analysis and RT-PCR validation indicated that miR-146b was significantly overexpressed and nuclear receptor co-activator 4 (NCOA4) suppressed in colons of C. difficile infected mice. We next developed a computational model that predicts the upregulation of miR-146b, downregulation of the PPARc co-activator NCOA4, and PPARc, leading to upregulation of IL-17. Oral treatment of C. difficile-infected mice with the PPARc agonist pioglitazone ameliorated colitis and suppressed pro-inflammatory gene expression. In conclusion, our data indicates that miRNA-146b and PPARc activation may be implicated in the regulation of Th17 responses and colitis in C. difficile-infected mice.en_US
dc.description.sponsorshipSupported in part by National Institutes of Health 5R01AT004308 to JB-R, NIAID Contract No. HHSN272201000056C to JB-R and funds from the Nutritional Immunology and Molecular Medicine Laboratory. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.subjectClostridium difficilen_US
dc.subjectColonen_US
dc.subjectGene expressionen_US
dc.subjectGene targetingen_US
dc.subjectImmune responseen_US
dc.subjectLesionsen_US
dc.subjectMicroRNAen_US
dc.subjectT Cellsen_US
dc.titleModeling the Role of Peroxisome Proliferator-Activated Receptor c and MicroRNA-146 in Mucosal Immune Responses to Clostridium difficileen_US
dc.typeArticle - Refereeden_US
dc.identifier.urlhttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047525en_US
dc.date.accessed2014-05-13en_US
dc.title.serialPLoS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0047525


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