Navegando por Palavras-chave "Flagelina"
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- ItemSomente MetadadadosPapel do inflamassoma NLRC4 na indução e secreção de IL-1alpha em resposta à flagelina(Universidade Federal de São Paulo, 2014-08-29) Freitas, Carla Longo de [UNIFESP]; Bortoluci, Karina Ramalho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The flagellin monomer, structural protein that composes a subunit of bacterial flagellum, is recognized by the innate immune system by TLR5, but is transported to cytosol by secretion system of pathogenic bacterias where it is capable to active the NAIP5/NLRC4 inflammasome. The NAIP5/NLRC4 inflammasome can also contain the adaptor molecule ASC, inducing particular responses according to the formed complex. NLRC4 inflammasomes that recruit the adaptor molecule ASC induce autoproteolytic cleavege of caspase-1 and IL-1β and IL-18 pro-cytokines processing. In a different manner, NLRC4 ASC-independent inflammasomes activate caspase-1 but do not induce an autoproteolytic cleavage, leading to a rapid cell death by pyroptosis. In the last years, our group has been studying new effector mechanisms triggered by cytosolic flagellin, such as the release of the damage associated molecular pattern, IL-1α. Recent data suggest inflammasomes are involved in IL-1α secretion, however, little is known about this cytokine regulation. In this work, we demonstrate that cytosolic flagellin is capable of induce IL-1α secretion in a NLRC4, ASC and caspase-1 partially dependent manner. Interestingly, cytosolic flagellin also was capable of induce IL-1α production in cells lysates. However, this effect was not altered in the absence of NLRC4. Furthermore the induction of IL-1α secretion in response to cytosolic flagellin was inhibited in the presence of CA074-Me, pharmacological inhibitor of cathepsin B,a lysossomal enzyme, suggesting that more than one pathway can be triggered by cytosolic flagellin to induce production of IL-1α. Finally, we performed an assay that allowed us to evaluate secretion of IL-1α and cellular viability all together. Our data suggest that induction of IL-1α secretion in response to cytosolic flagellin envolves different molecular machineries. Still, secretion of IL-1α seems to preceed cell detah or occurs in a cell death independent manner, a fact that defy previous data tha indicate passive release of this cytokine by dead cells.
- ItemSomente MetadadadosProteinas de superficie bacteriana como apresentadoras de peptideos heterologos(Universidade Federal de São Paulo (UNIFESP), 1999) Pereira, Catia Mendes [UNIFESP]