Estudo da influência da infecção pelo Mycobacterium tuberculosis sobre a replicação do HIV e a imunidade celular em associação com os polimorfismos dos genes tlr2 e tlr4

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Associação de polimorfismos nos genes TLR2 e TLR4 com risco de câncer colorretal esporádico e influência na expressão gênica

Pós-graduação em Genética - IBILCE

Papel de RAGE e TLR4 na modulação da resposta imune inflamatoria em PBMC de pacientes diabéticos e não diabéticos: (estudo in vitro)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Polimorfismos gênicos de citocinas e receptores envolvidos no processo inflamatório da carcinogênese gástrica e alterações nos níveis de expressão gênica

Pós-graduação em Genética - IBILCE

Expressão de citoceratinas de padrão basal (CK5/6), luminal (CK8/18) e actina de músculo liso (1A4) em carcinoma de mama

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Monocytes from Pregnant Women with Pre-Eclampsia are Polarized to a M1 Phenotype

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Associação entre expressão de receptores TLR2 e TLR4 e produção de TNF-alpha e IL-10 por monócitos de gestantes portadoras de pré-eclâmpsia

Preeclampsia (PE) is a pregnancy specific syndrome characterized by a systemic inflammatory response, with higher intensity than that observed in normal pregnancy. Cells of the immune system, such as monocytes and granulocytes are endogenously activated and secrete high levels of free radicals and inflammatory cytokines. The objective of this study was to assess the activation state of monocytes from pregnant women with preeclampsia by endogenous expression of TLR2 e TLR4 receptors and to correlate the expression of TLR2 and TLR4 on monocytes surface of pregnant women with PE with the production of tumor necrosis factor-alpha (TNF- and interleukin-10 (IL-10) by these cells stimulated or not with peptidoglycan (PG) and lipopolysaccharide (LPS), as agonists agents of TLR2 and TLR4, respectively. We evaluated 15 pregnant women with PE, 15 normotensive pregnant women (NT) and 15 non-pregnant (NP). Peripheral blood monocytes were incubates in the presence or absence of LPS or PG. The supernatant obtained after 18h of culture was aspirated and used for TNF- and IL-10 determination by enzyme immunoassay (ELISA). The endogenous expression of TLR2 and TLR4 receptors was evaluated by flow cytometry. Our results showed significant highly concentrations of TNF- and TLR4 expression in monocytes of preeclamptic women when compared with NT and NP. Normal pregnant women presented higher levels of IL-10 in comparison with PE and NP groups. TLR2 expression was similar in the three groups studied. Therefore, our study highlights the important role of TLR4 in PE and the consequent high production of TNF- by monocytes of these patients, as well as the potential mechanism involving low levels of IL-10 in the pathophysiology of the disease. These observations demonstrate the strong link between the pathology of PE and the immune system of these patients

Análises histopatológicas, bioquímicas e moleculares sobre os efeitos da interação entre o uso de altas doses de decanoato de nadrolona e o exercício resistido durante a fase pós-púbere sobre a próstata de ratos em processo de envelhecimento

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The modulatory effects of caffeic acid on human monocytes and its involvement in propolis action

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Involvement of major components from sporothrix schenckii cell wall in the caspase-1 activation, nitric oxide and cytokines production during experimental sporotrichosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Papel dos receptores TLR2 e TLR4 na produção de citocinas em pacientes chagásicos crônicos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Relações filogenéticas do gênero Apistogramma (Teleostei, Cichlidae) e filogeografia da espécie Apistogramma agassizi

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

ROLE of TLR2 and TLR4 on human neutrophil functions against Paracoccidioides brasiliensis

In paracoccidioidomycosis, a systemic mycosis caused by the fungus Paracoccidioides brasiliensis (Pb), studies have focused on the role of neutrophils that are involved in the primary response to the fungus. Neutrophil functions are regulated by pro- and anti-inflammatory cytokines. Molecular mechanisms involved in this process are not fully understood, but there are strong evidences about the involvement of toll-like receptors (TLRs). We aimed at evaluating TLR2 and TLR4 expression on human neutrophils activated by GM-CSF, IL-15, TNF-alpha or IFNgamma and challenged with a virulent strain of P. brasiliensis (Pb18). Moreover, we asked if these receptors have a role on fungicidal activity, H(2)O(2) and IL-6, IL-8, TNFalpha and IL-10 production, by activating and challenging cells. All cytokines increased TLR2 and TLR4 expression. Pb18 also increased TLR2 expression, inducing an additional cytokine effect. on the contrary, it inhibited TLR4 expression. All cytokines increased neutrophil fungicidal activity and H(2)O(2) production; however, this process was not associated with TLR2 or TLR4. Neutrophil activation by GMCSF and TNF-alpha resulted in a significant increase of IL-8 production, while IL-15 and IFN-alpha have no effect. Pb18 also augmented IL-8 expression, inducing an additional effect to that of cytokines. None of the cytokines activated neutrophils by releasing IL-10. This cytokine was only detected after Pb18 challenge. Interestingly, IL-8 and IL-10 production involved TLR2 and mainly TLR4 modulation. The present results suggest that Pb18 interaction with neutrophils through TLR2 and TLR4 with consequent IL-8 and IL-10 production may be considered a pathogenic mechanism in paracoccidioidomycosis.

Role of TLR2 and TLR4 in Human Neutrophil Functions Against Paracoccidioides brasiliensis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Late-onset sepsis: Epidemiology, evaluation, and outcome

Late-onset neonatal sepsis is a common serious problem in preterm infants in neonatal intensive care units. Diagnosis can be difficult because clinical manifestations are not specific and none of the available laboratory tests can be considered an ideal marker. For this reason, a combination of markers has been proposed. Complete blood count and acute-phase reactants evaluated together help in diagnosis. C-reactive protein is a specific but late marker, and procalcitonin has proven accurate, although it is little studied in newborns. Blood, cerebrospinal fluid, and urine cultures always should be obtained when late-onset sepsis is suspected. Blood culture, the gold standard in diagnosis, is highly sensitive but needs up to 48 hours to detect microbial growth. Various cytokines have been investigated as early markers of infection, but results are not uniform. Other diagnostic tests that offer promise include: neutrophil surface markers, granulocyte colony-stimulating factor, toll-like receptors, and nuclear factor kappa B. The greatest hope for quick and accurate diagnosis lies in molecular biology, using real time polymerase chain reaction combined withDNAmicroarray. Sepsis and meningitis may affect both the short- and long-term prognosis for newborns. Mortality in neonatal meningitis has been reduced in recent years, but short-term complications and later neurocognitive sequelae remain. Late-onset sepsis significantly increases preterm infant mortality and the risk of cerebral lesions and neurosensory sequelae, including developmental difficulties and cerebral palsy. Early diagnosis of late-onset sepsis contributes to improved neonatal prognosis, but the outcome remains far from satisfactory. © 2010 by the American Academy of Pediatrics.