NIELS OLSEN SARAIVA CAMARA
Projetos de Pesquisa
Unidades Organizacionais
BMI, ICB - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
Agora exibindo 1 - 2 de 2
- NLRP3 gain-of-function in CD4(+) T lymphocytes ameliorates experimental autoimmune encephalomyelitis(2019) BRAGA, Tarcio Teodoro; BRANDAO, Wesley Nogueira; AZEVEDO, Hatylas; TERRA, Fernanda Fernandes; MELO, Amanda Campelo L.; PEREIRA, Felipe Valenca; ANDRADE-OLIVEIRA, Vinicius; HIYANE, Meire Ioshie; PERON, Jean Pierre S.; CAMARA, Niels Olsen SaraivaNLRP3 inflammasome [NLR (nucleotide-binding domain, leucine-rich repeat containing protein) Pyrin-domain-containing 3] functions as an innate sensor of several PAMPs and DAMPs (pathogen- and damage-associated molecular patterns). It has been also reported as a transcription factor related to Th2 pattern, although its role in the adaptive immunity has been controversial, mainly because the studies were performed using gene deletion approaches. In the present study, we have investigated the NLRP3 gain-of-function in the context of encephalomyelitis autoimmune disease (EAE), considered to be a Th1- and Th 17-mediated disease. We took advantage of an animal model with NLRP3 gain-of-function exclusively to T CD4(+) lymphocytes (CD4CreNLRP3fl/fl). These mice presented reduced clinical score, accompanied by less infiltrating T CD4(+) cells expressing both IFN-gamma and 1L-17 at the central nervous system (CNS) during the peak of the disease. However, besides NLRP3 gain-of-function in lymphocytes, these mice lack NLRP3 expression in non-T CD4(+) cells. Therefore, in order to circumvent this deficiency, we transferred naive CD4- T cells from WT, NLRP3-/- or CD4CreNLRP3fl/fl into Rag-1-/- mice and immunized them with MOG(35-55). Likewise, the animals repopulated with CD4CreNLRP3fl/fl T CD4+ cells presented reduced clinical score and decreased IFN-gamma production at the peak of the disease. Additionally, primary effector CD4(+) T cells derived from these mice presented reduced glycolytic profile, a metabolic profile compatible with Th2 cells. Finally, naive CD4(+) T cells from CD4CreNLRP3fl/fl mice under a Th2-related cytokine milieu cocktail exhibited in vitro an increased IL-4 and IL-13 production. Conversely, naive CD4(+) T cells from CD4CreNLRP3fl/fl mice under Th1 differentiation produced less IFN-gamma and T-bet. Altogether, our data evidence that the NLRP3 gain-of-function promotes a Th2-related response, a pathway that could be better explored in the treatment of multiple sclerosis.
- TLR2 and TLR4 play opposite role in autophagy associated with cisplatin-induced acute kidney injury(2018) ANDRADE-SILVA, Magaiver; CENEDEZE, Marcos Antonio; PERANDINI, Luiz Augusto; FELIZARDO, Raphael Jose Ferreira; WATANABE, Ingrid Kazue Mizuno; AGUDELO, Juan Sebastian Henao; CASTOLDI, Angela; GONCALVES, Giselle Martins; ORIGASSA, Clarice Silvia Taemi; SEMEDO, Patricia; HIYANE, Meire Ioshie; FORESTO-NETO, Orestes; MALHEIROS, Denise Maria Avancini Costa; REIS, Marlene Antonia; FUJIHARA, Clarice Kazue; ZATZ, Roberto; PACHECO-SILVA, Alvaro; CAMARA, Niels Olsen Saraiva; ALMEIDA, Danilo Candido deAcute kidney injury (AKI) is considered an inflammatory disease in which toll-like receptors (TLRs) signaling pathways play an important role. The activation of TLRs results in production of several inflammatory cytokines leading to further renal damage. In contrast, TLRs are key players on autophagy induction, which is associated with a protective function on cisplatin-induced AKI. Hence, the present study aimed to evaluate the specific participation of TLR2 and TLR4 molecules on the development of cisplatin-induced AKI. Complementarily, we also investigated the link between TLRs and heme oxygenase-1 (HO-1), a promisor cytoprotective molecule. First, we observed that only the absence of TLR2 but not TLR4 in mice exacerbated the renal dysfunction, tissue injury and mortality rate, even under an immunologically privileged microenvironment. Second, we demonstrated that TLR2 knockout (KO) mice presented lower expression of autophagy-associated markers when compared with TLR4 KO animals. Similar parameter was confirmed in vitro, using tubular epithelial cells derived from both KO mice. To test the cross-talking between HO-1 and TLRs, hemin (an HO-1 internal inducer) was administrated in cisplatin-treated TLR2 and TLR4 KO mice and it was detected an improvement in the global renal tissue parameters. However, this protection was less evident at TLR2 KO mice. In summary, we documented that TLR2 plays a protective role in cisplatin-induced AKI progression, in part, by a mechanism associated with autophagy up-regulation, considering that its interplay with HO-1 can promote renal tissue recover.