ANA IOCHABEL SOARES MORETTI
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- The role of nitric oxide in the epigenetic regulation of THP-1 induced by lipopolysaccharide(2016) RIOS, Ester Correia Sarmento; LIMA, Thais Martins de; MORETTI, Ana Iochabel Soares; SORIANO, Francisco GarciaAims: Changes in the gene expression are one of the molecular events involved in the Systemic of Inflammatory Response Syndrome during sepsis. The preconditioning with low doses of lipopolysaccharide (LPS) reduces the expression of pro-inflammatory genes leading to less tissue damage and better outcome. This hyporesponsive state called tolerance is associated to alterations in chromatin structure and nitric oxide (NO) production. In the current study, we demonstrated that tolerance induced by LPS was found to be NO-dependent and related to epigenetic changes. Main methods: THP-1 cells were cultivated in RPMI medium(Control), submitted to tolerance (500 ng/mL of LPS 24 h before challenge with 1000 ng/mL of LPS during 24 h Tolerant group) and challenge (1000 ng/mL of LPS during 24 h Directly challenged group). The analyses performed were: cytokines production, histone acetyl transferases/histone deacetylases (HAT/HDAC) activity, nitrosylation of HDAC-2 and -3, expression of acetylated histones H3 and H4. HDAC and Nitric Oxide Synthases (NOS) activities were inhibited with 30 mM trichostatin (TSA) and 100 mu M LNAME, respectively. Key findings: Administration of low doses of LPS repressed the production of IL-6 and IL-10, however this effect was abolished with the inhibition of NOS activity and by TSA in the case of IL-10. Tolerance modulates the activity of HAT and, consequently, the acetylation of histones H3 and H4. Inhibition of NO decreases acetylation of Histones. The HDACs 2 and 3 were nitrosylated after the tolerance induction. Significance: The tolerance to LPS regulates the cytokine production by modulating chromatin structure and this event is NO dependent.
- Low level laser therapy reduces acute lung inflammation without impairing lung function(2016) CURY, Vivian; LIMA, Thais Martins de; PRADO, Carla Maximo; PINHEIRO, Nathalia; ARIGA, Suely K. K.; BARBEIRO, Denise F.; MORETTI, Ana I.; SOUZA, Heraldo P.Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm(2). Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-alpha, IL-1 beta, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx [GRAPHICS] and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery.
conferenceObject Effect of low level laser therapy on acute lung injury(2012) CURY, Vivian; LIMA-SALGADO, Thais; PINHEIRO, Natalia; PRADO, Carla Maximo; ASSIS, Livia; MORETTI, Ana Iochabel; SOUZA, Heraldo PossoloLow level laser therapy (LLLT) is prescribed as adjuvant therapy for inflammatory diseases. Hence, we examined whether LLLT may ameliorate acute lung injury (ALI) induced by intratracheal LPS instillation. C57 black mice (n=10 per group) were treated with intratracheal LPS (5mg/kg) or PBS. Six hours after instillation, two groups (PBS and LPS) were irradiated with laser at 660 nm, power output 30mW, fluency 10J/cm2. We observed a marked decrease in the number of cells recovered by bronchoalveolar lavage in LPS + LLLT animals compared to LPS alone (2.0±0.8 x 4.4±1.3, respectively p<0.05). LLLT also decreased the number of inflammatory cells infiltrated in lung interstitium (49.6±3.15 x 71.8±3.92), p<0.05). There was also a decrease in the expression of F4/80 (macrophage surface marker) and MCP-1 (monocyte chemoattractant protein-1), detected by quantitative PCR, in animals submitted to LPS + LLLT, when compared to animals that received only LPS. A marked decrease in cytokines secretion (IL1β, TNFα, IL6, IL10) was also observed in LPS+LLLT group. No difference was observed in animals that received PBS, regardless of LLLT. Therefore, LLLT decreases pulmonary inflammatory cell infiltration, cytokines and chemokines secretion in an experimental model of ALI, supporting the notion that laser therapy attenuates inflammatory intensity, what can contribute to accelerate ALI resolution.- PGC-1 alpha Expression Is Increased in Leukocytes in Experimental Acute Pancreatitis(2014) LLIMONA, Flavia; LIMA, Thais Martins de; MORETTI, Ana Iochabel; THEOBALDO, Mariana; JUKEMURA, Jose; VELASCO, Irineu Tadeu; MACHADO, Marcel C. C.; SOUZA, Heraldo PossoloSevere acute pancreatitis (AP) induces a systemic inflammatory disease that is responsible for high mortality rates, particularly when it is complicated by infection. Therefore, differentiating sepsis from the systemic inflammation caused by AP is a serious clinical challenge. Considering the high metabolic rates of leukocytes in response to stress induced by infection, we hypothesized that the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1 alpha), a master regulator of mitochondrial biogenesis and function, would be distinctly expressed during inflammation or infection and, therefore, could constitute a useful marker to differentiate between these two conditions. Rats were subjected to injection of taurocholate into the main pancreatic duct, which caused a severe AP with high amylase levels and white blood cell counts. In these animals, a marked increase in PGC-1 alpha mRNA levels in circulating leukocytes was observed 48 h after the surgical procedure, a time when bacteremia is present. Antibiotic treatment abolished PGC-1 alpha up-regulation. Moreover, PGC-1 alpha expression was higher in peritoneal macrophages from animals subjected to a bacterial insult (cecal ligation and puncture) than in animals with AP. In isolated macrophages, we also observed that PGC-1 alpha expression is more prominent in the presence of a phagocytic stimulus (zymosan) when compared to lipopolysaccharide-induced aseptic inflammation. Moreover, abolishing PGC-1 alpha expression with antisense oligos impaired zymosan phagocytosis. Together, these findings suggest that PGC-1 alpha is differentially expressed during aseptic inflammation and infection and that it is necessary for adequate phagocytosis. These results could be useful in developing new tests for differentiating infection from inflammation for clinical purposes in patients with AP.
conferenceObject PGC-1 alpha is a Valuable Tool to Differentiate Inflammation From Infection in Acute Pancreatitis(2012) LLIMONA, F.; LIMA-SALGADO, T. M.; MORETTI, A. L.; THEOBALDO, M.; JUKEMURA, J.; MACHADO, M. C. C.; VELASCO, I. T.; SOUZA, H. P.Background: Differentiate sepsis from the systemic inflammation caused by AP remains a clinical challenge. We hypothesized that transcription coactivator PGC-1>, a regulator of mitochondrial biogenesis and function, would be distinctly expressed during inflammation or infection, being useful to differentiate these two conditions. Methods: Acute pancreatitis(AP) was induced by retrograde injection o,5 ml of 5% sodium taurocholate into the main pancreatic duct.. PGC-1> mRNA.was evaluated by using a quantitayive Real-time PCR Macrophages were obtained by washing the peritoneum with PBS and placed in culture for 2h. and exposed to lipopolysaccharide, zymosan or vehicle. In another set of experiments, macrophages were transfected with antisense against PGC-1> Cecal ligation puncture (CLP) was used to establish a model of infected peritonitis. Results: In AP animals a marked increase in PGC-1> mRNA levels in circulating leukocytes was observed 48h after the surgical procedure, a time when bacteremia is present. Antibiotic treatment abolished PGC-1> up-regulation. Moreover, PGC-1> expression was higher in peritoneal macrophages from animals submitted to a bacterial insult (CLP) than in animals with acute pancreatitis .In macrophages, we could observe that PGC-1> expression is more prominent in the presence of a phagocytic stimulus (zymosan) compared to an aseptic inflammation induce by lipopolysaccharide. Moreover, abolishing PGC-1> expression with antisense impaired zymosan phagocytosis. Conclusion: Together these findings suggest that PGC-1> is differentially expressed during aseptic inflammation and infection and that it is necessary for adequate phagocytosis. These results could be useful in developing new tests for differentiating infection from inflammation in patients with acute pancreatitis.