TESE DE DOUTORADO - PROGRAMA DE PÓS-GRADUAÇÃO EM REDE - REDE DE BIODIVERSIDADE E BIOTECNOLOGIA DA AMAZÔNIA LEGAL/CCBS

URI Permanente para esta coleçãohttps://tedebc-teste.ufma.br/handle/tede/1260

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Estudo dos mecanismos associados aos efeitos da tioredoxina derivada de Escherichia coli na sepse
(Universidade Federal do Maranhão, 2018-11-22) MENDES, Saulo José Figueiredo; SILVA, Luís Cláudio Nascimento da; 061482494-05; http://lattes.cnpq.br/6016850820500623; FERNANDES, Elizabeth Soares; 033401406-93; http://lattes.cnpq.br/9631573633970523; FERNANDES, Elizabeth Soares; 033401406-93; http://lattes.cnpq.br/9631573633970523
Thioredoxin (Trx) is a redox protein produced by all species, from bacteria to humans. It role as an antioxidant molecule is well known; however, its regulatory actions in the host are less understood. Evidences suggest this protein may be part of the bacteria anti-virulence strategy to evade the host immune system. Reduced human Trx activates transient receptor potential canonical 5 (TRPC5) in inflammation, but there is no evidence of whether these receptors mediate bacterial Trx effects in the host. Importantly, TRPC5 can form functional complexes with other subunits such as TRPC4. Herein, E. coli-derived Trx induced mortality in lipopolysaccharide (LPS)-injected mice, accompanied by reduction of leukocyte accumulation, regulation of cytokine release into the peritoneum, and impairment of peritoneal macrophage-mediated phagocytosis. Dual TRPC4/TRPC5 blockade by ML204 increased mortality and hypothermia in Trx-treated LPS mice, but preserved macrophage´s ability to phagocytose. TRPC5 deletion did not alter body temperature, but promoted additional accumulation of peritoneal leukocytes and inflammatory mediator release in Trx-administered LPS mice. Trx diminished macrophage-mediated phagocytosis in wild type but not TRPC5 knockout animals. TRPC5 ablation did not affect LPS-induced responses. However, ML204 caused mortality associated with exacerbated hypothermia and decreased peritoneal leukocyte numbers and cytokines in LPS-injected mice. These results suggest that bacterial Trx 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 recep

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Navegando TESE DE DOUTORADO - PROGRAMA DE PÓS-GRADUAÇÃO EM REDE - REDE DE BIODIVERSIDADE E BIOTECNOLOGIA DA AMAZÔNIA LEGAL/CCBS por Assunto "Bacterial thioredoxin, SIRS, LPS immune response, TRPC5."