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
7 resultados
Resultados de Busca
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- Hypoxia enhances ILC3 responses through HIF-1 alpha-dependent mechanism(2021) FACHI, J. L.; PRAL, L. P.; SANTOS, J. A. C. dos; CODO, A. C.; OLIVEIRA, S. de; FELIPE, J. S.; ZAMBOM, F. F. F.; CAMARA, N. O. S.; VIEIRA, P. M. M. M.; COLONNA, M.; VINOLO, M. A. R.Group 3 innate lymphoid cells (ILC3) have a prominent role in the maintenance of intestine mucosa homeostasis. The hypoxia-inducible factor (HIF) is an important modulator of immune cell activation and a key mechanism for cellular adaptation to oxygen deprivation. However, its role on ILC3 is not well known. In this study, we investigated how a hypoxic environment modulates ILC3 response and the subsequent participation of HIF-1 signaling in this process. We found increased proliferation and activation of intestinal ILC3 at low oxygen levels, a response that was phenocopied when HIF-1 alpha was chemically stabilized and was reversed when HIF-1 was blocked. The increased activation of ILC3 relied on a HIF-1 alpha-dependent transcriptional program, but not on mTOR-signaling or a switch to glycolysis. HIF-1 alpha deficiency in RORyt compartment resulted in impaired IL-17 and IL-22 production by ILC3 in vivo, which reflected in a lower expression of their target genes in the intestinal epithelium and an increased susceptibility to Clostridiodes difficile infection. Taken together, our results show that HIF-1 alpha activation in intestinal ILC3 is relevant for their functions in steady state and infectious conditions.
- Butyrate Attenuates Lung Inflammation by Negatively Modulating Th9 Cells(2019) VIEIRA, Raquel de Souza; CASTOLDI, Angela; BASSO, Paulo Jose; HIYANE, Meire Ioshie; CAMARA, Niels Olsen Saraiva; ALMEIDA, Rafael RibeiroTh9 cells orchestrate allergic lung inflammation by promoting recruitment and activation of eosinophils and mast cells, and by stimulating epithelial mucus production, which is known to be mainly dependent on IL-9. These cells share developmental pathways with induced regulatory T cells that may determine the generation of one over the other subset. In fact, the FOXP3 transcription factor has been shown to bind il9 locus and repress IL-9 production. The microbiota-derived short-chain fatty acids (SCFAs) butyrate and propionate have been described as FOXP3 inducers and are known to have anti-inflammatory properties. While SCFAs attenuate lung inflammation by inducing regulatory T cells and suppressing Th2 responses, their effects on Th9 cells have not been addressed yet. Therefore, we hypothesized that SCFAs would have a protective role in lung inflammation by negatively modulating differentiation and function of Th9 cells. Our results demonstrated that butyrate is more effective than propionate in promoting FOXP3 expression and IL-9 repression. In addition, propionate was found to negatively impact in vitro differentiation of IL-13-expressing T cells. Butyrate treatment attenuated lung inflammation and mucus production in OVA-challenged mice, which presented lower frequency of lung-infiltrated Th9 cells and eosinophils. Both Th9 cell adoptive transfer and IL-9 treatment restored lung inflammation in butyrate-treated OVA-challenged mice, indicating that the anti-inflammatory effects of butyrate may rely on suppressing Th9-mediated immune responses.
- Nephropathy in Hypertensive Animals Is Linked to M2 Macrophages and Increased Expression of the YM1/Chi3l3 Protein(2019) CAVALCANTE, Paula Andrea Malveira; ALENINA, Natalia; BUDU, Alexandre; FREITAS-LIMA, Leandro Ceotto; ALVES-SILVA, Thais; AGUDELO, Juan Sebastian Henao; QADRI, Fatimunnisa; CAMARA, Niels Olsen Saraiva; BADER, Michael; ARAUJO, Ronaldo CarvalhoMacrophages contribute to a continuous increase in blood pressure and kidney damage in hypertension, but their polarization status and the underlying mechanisms have not been clarified. This study revealed an important role for M2 macrophages and the YM1/Chi3l3 protein in hypertensive nephropathy in a mouse model of hypertension. Bone marrow cells were isolated from the femurs and tibia of male FVB/N (control) and transgenic hypertensive animals that overexpressed the rat form of angiotensinogen (TGM(rAOGEN)123, TGM123-FVB/N). The cells were treated with murine M-CSF and subsequently with LPS+IFN-gamma to promote their polarization into M1 macrophages and IL-4+IL-13 to trigger the M2 phenotype. We examined the kidneys of TGM123-FVB/N animals to assess macrophage polarization and end-organ damage. mRNA expression was evaluated using real-time PCR, and protein levels were assessed through ELISA, CBA, Western blot, and immunofluorescence. Histology confirmed high levels of renal collagen. Cells stimulated with LPS+IFN-gamma in vitro showed no significant difference in the expression of CD86, an M1 marker, compared to cells from the controls or the hypertensive mice. When stimulated with IL-4+IL-13, however, macrophages of the hypertensive group showed a significant increase in CD206 expression, an M2 marker. The M2/M1 ratio reached 288%. Our results indicate that when stimulated in vitro, macrophages from hypertensive mice are predisposed toward polarization to an M2 phenotype. These data support results from the kidneys where we found an increased infiltration of macrophages predominantly polarized to M2 associated with high levels of YM1/Chi3l3 (91,89%), suggesting that YM1/Chi3l3 may be a biomarker of hypertensive nephropathy.
- The lack of PI3K gamma favors M1 macrophage polarization and does not prevent kidney diseases progression(2018) AMANO, Mariane T.; CASTOLDI, Angela; ANDRADE-OLIVEIRA, Vinicius; LATANCIA, Marcela T.; TERRA, Fernanda F.; CORREA-COSTA, Matheus; BREDA, Cristiane N. S.; FELIZARDO, Raphael J. F.; PEREIRA, Welbert O.; SILVA, Marina B. da; MIYAGI, Mariana Y. S.; AGUIAR, Cristhiane F.; I, Meire Hiyane; SILVA, Joao S.; MOURA, Ivan C.; CAMARA, Niels O. S.Acute kidney injury (AKI) and chronic kidney disease (CKD) are major concerns in worldwide public health, and their pathophysiology involves immune cells activation, being macrophages one of the main players of both processes. It is suggested that metabolic pathways could contribute to macrophage modulation and phosphatidylinositol-3 kinase (PI3K) pathway was shown to be activated in kidneys subjected to ischemia and reperfusion as well as unilateral ureteral obstruction (UUO). Although PI3K inhibition is mostly associated with anti-inflammatory response, its use in kidney injuries has been shown controversial results, which indicates the need for further studies. Our aim was to unveil the role of PI3K gamma in macrophage polarization and in kidney diseases development. We analyzed bone-marrow macrophages polarization from wild-type (WT) and PI3K gamma knockout (PI3K KO) animals. We observed increased expression of M1 (CD86, CCR7, iNOS, TNF, CXCL9, CXCL10, IL-12 and IL-23) and decreased of M2 (CD206, Arg-1, FIZZ1 and YM1) markers in the lack of PI3K gamma. And this modulation was accompanied by higher levels of inflammatory cytokines in PI3K KO M1 cells. PI3K KO mice had increased M1 in steady state kidneys, and no protection was observed in these mice after acute and chronic kidney insults. On the contrary, they presented higher levels of protein-to-creatinine ratio and Kim-1 expression and increased tubular injury. In conclusion, our findings demonstrated that the lack of PI3K gamma favors M1 macrophages polarization providing an inflammatory-prone environment, which does not prevent kidney diseases progression.
- Physical exercise contributes to cisplatin-induced nephrotoxicity protection with decreased CD4+T cells activation(2018) MIYAGI, Mariana Yasue Saito; LATANCIA, Marcela Teatin; TESTAGROSSA, Leonardo Abreu; ANDRADE-OLIVEIRA, Vinicius de; PEREIRA, Welbert Oliveira; HIYANE, Meire Ioshie; ENJIU, Lucas Maceratesi; PISCIOTTANO, Marcus; SEELAENDER, Marilia Cerqueira Leite; CAMARA, Niels Olsen Saraiva; AMANO, Mariane TamiCisplatin is a chemotherapy used to treat different types of cancer, such as testicular, bladder and head and neck. Physical exercise has been shown to improve cancer therapy and recently, it was demonstrated to be able to diminish side effects such as acute kidney injury (AKI), a common side effect in cisplatin treatment. In both cases, the modulation of inflammatory cytokines seems to be one of the mechanisms, but little is known about the immune cells in this process. Here, we investigated the role of CD4 + T cells in the AKI protection by physical exercise. We subjected C57B16 mice to long-term physical exercise (EX) before cisplatin treatment. Sedentary groups were used as control (CT). We confirmed that physical exercise decreased AKI by evaluating creatinine and Kim-1 levels, in the serum and kidney respectively. Analyzing the organs weight, we noticed a decrease in sedentary (CIS) and exercised (CIS-EX) cisplatin treated groups. Epididymal and brown adipose tissue weight were decreased in cisplatin treated subjects in comparison to untreated groups, as well as liver and spleen. We then investigated the profile of CD4 + T cells in the spleen and we observed increased levels of Tregs and CD4 + CD25 + cells in CIS group, while CIS-EX presented similar amounts as control groups. Analyzing the kidney lymph nodes, we noticed a decrease of CD4 + cells in both CIS and CIS-EX group. However, a more activated phenotype (CD69 + and CD25 + ) was observed in CIS groups in comparison to CIS-EX group, as well as the presence of Tregs. We then investigated the production of cytokines by these cells and no difference among the groups was observed in cytokines production in splenic CD4 + T cells. However, a clear increase in TNF and IL-10 production was observed in CD4 + T cells from lymph nodes, while CIS-EX group presented similar levels as the control groups. We confirmed that physical exercise was able to diminish cisplatin-induced AKI with concomitant decrease in CD4 + T cell activation.
- CCR2 contributes to the recruitment of monocytes and leads to kidney inflammation and fibrosis development(2018) BRAGA, Tarcio Teodoro; CORREA-COSTA, Matheus; SILVA, Reinaldo Correia; CRUZ, Mario Costa; HIYANE, Meire Ioshie; SILVA, Joao Santana da; PEREZ, Katia Regina; CUCCOVIA, Iolanda Midea; CAMARA, Niels Olsen SaraivaChemokines are a large family of proteins that, once associated to its receptor on leukocytes, stimulate their movement and migration from blood to tissues. Once in the tissue, immune cells trigger inflammation that, when uncontrolled, leads to fibrosis development. Among the immune cells, macrophages take a special role in fibrosis formation, since macrophage depletion reflects less collagen deposition. The majority of tissue macrophages is derived from monocytes, especially monocytes expressing the chemokine receptor CCR2. Here, we investigated the role of infiltrating CCR2(+) cells in the development of fibrosis, and specifically, the dynamic of infiltration of these cells into kidneys under chronic obstructive lesion. Using liposome-encapsulated clodronate, we observed that macrophage depletion culminated in less collagen deposition and reduced chemokines milieu that were released in the damaged kidney after obstructive nephropathy. We also obstructed the kidneys of CCL3(-/-), CCR2(-/-), CCR4(-/-), CCR5(-/-), and C57BL/6 mice and we found that among all animals, CCR2(-/-) mice demonstrated the more robust protection, reflected by less inflammatory and Th17-related cytokines and less collagen formation. Next we evaluated the dynamic of CCR2(+/rfp) cell infiltration and we observed that they adhere onto the vessels at early stages of disease, culminating in increased recruitment of CCR2(+/rfp) cells at later stages. On the other hand, CCR2(rfp/rfp) animals exhibited less fibrosis formation and reduced numbers of recruited cells at later stages. We have experimentally demonstrated that inflammatory CCR2(+) cells that reach the injured kidney at initial stages after tissue damage are responsible for the fibrotic pattern observed at later time points in the context of UUO.
- Mesenchymal stromal cells modulate gut inflammation in experimental colitis(2018) AGUIAR, Cristhiane Favero de; CASTOLDI, Angela; ANDRADE-OLIVEIRA, Vinicius; IGNACIO, Aline; CUNHA, Flavia Franco da; FELIZARDO, Raphael Jose Ferreira; BASSI, Enio Jose; CAMARA, Niels Olsen Saraiva; ALMEIDA, Danilo Candido deInflammatory bowel diseases (IBDs) affect millions of people worldwide and their frequencies in developed countries have increased since the twentieth century. In this context, there is an intensive search for therapies that modulate inflammation and provide tissue regeneration in IBDs. Recently, the immunomodulatory activity of adipose tissue-derived mesenchymal stromal cells (ADMSCs) has been demonstrated to play an important role on several immune cells in different conditions of inflammatory and autoimmune diseases. In this study, we explored the immunomodulatory potential of ADMSC in a classical model of DSS-induced colitis. First, we found that treatment of mice with ADMSC ameliorated the severity of DSS-induced colitis, reducing colitis pathological score and preventing colon shortening. Moreover, a prominent reduction of pro-inflammatory cytokines levels (i.e., IFN-gamma, TNF-alpha, IL-6 and MCP-1) was observed in the colon of animals treated with ADMSC. We also observed a significant reduction in the frequencies of macrophages (F4/80(+)CD11b(+)) and dendritic cells (CD11c(+)CD103(+)) in the intestinal lamina propria of ADMSC-treated mice. Finally, we detected the up-regulation of immunoregulatory-associated molecules in intestine of mice treated with ADMSCs (i.e., elevated arginase-1 and IL-10). Thus, this present study demonstrated that ADMSC modulates the overall gut inflammation (cell activation and recruitment) in experimental colitis, providing support to the further development of new strategies in the treatment of intestinal diseases.