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Reduced human Trx activates transient receptor potential canonical 5 (TRPC5) in inflammation, but there is no evidence of whether these receptors mediate bacterial thioredoxin effects in the host. Importantly, TRPC5 can form functional complexes with other subunits such as TRPC4. Herein, <jats:italic>E. coli<\/jats:italic>\u2010derived thioredoxin induced mortality in lipopolysaccharide\u2010 (LPS\u2010) injected mice, accompanied by reduction of leukocyte accumulation, regulation of cytokine release into the peritoneum, and impairment of peritoneal macrophage\u2010mediated phagocytosis. Dual TRPC4\/TRPC5 blockade by ML204 increased mortality and hypothermia in thioredoxin\u2010treated LPS mice but preserved macrophage\u2019s ability to phagocytose. TRPC5 deletion did not alter body temperature but promoted additional accumulation of peritoneal leukocytes and inflammatory mediator release in thioredoxin\u2010administered LPS mice. Thioredoxin diminished macrophage\u2010mediated phagocytosis in wild\u2010type but not TRPC5 knockout animals. TRPC5 ablation did not affect LPS\u2010induced responses. However, ML204 caused mortality associated with exacerbated hypothermia and decreased peritoneal leukocyte numbers and cytokines in LPS\u2010injected mice. These results suggest that bacterial thioredoxin effects under LPS stimuli are mediated by TRPC4 and TRPC5, shedding light on the additional mechanisms of bacterial virulence and on the pathophysiological roles of these receptors.<\/jats:p>","DOI":"10.1155\/2018\/4904696","type":"journal-article","created":{"date-parts":[[2018,6,10]],"date-time":"2018-06-10T23:31:55Z","timestamp":1528673515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Transient Receptor Potential Canonical Channels 4 and 5 Mediate <i>Escherichia coli<\/i>\u2010Derived Thioredoxin Effects in Lipopolysaccharide\u2010Injected Mice"],"prefix":"10.1155","volume":"2018","author":[{"given":"Domingos M. S.","family":"Pereira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saulo J. 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