DENISE FREDIANI BARBEIRO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
LIM/51 - Laboratório de Emergências Clínicas, Hospital das Clínicas, Faculdade de Medicina
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses(2021) LOURENCO, Juliana D.; TEODORO, Walcy R.; BARBEIRO, Denise F.; VELOSA, Ana Paula P.; SILVA, Larissa E. F.; KOHLER, Julia B.; MOREIRA, Alyne R.; V, Marcelo Aun; SILVA, Isadora C. da; FERNANDES, Frederico L. A.; NEGRI, Elnara M.; GROSS, Jefferson L.; TIBERIO, Iolanda F. L. C.; ITO, Juliana T.; LOPES, Fernanda D. T. Q. S.Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, ROR gamma t, Foxp3, interleukin (IL)-6, -17, -10, and TGF-beta was assessed by RT-qPCR. IL-6, -17, -10, and TGF-beta levels were determined by ELISA. We observed increased STAT3, ROR gamma t, Foxp3, IL-6, and TGF-beta gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, ROR gamma t, IL-6, and TGF-beta gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.
- Gastrin-Releasing Peptide Receptor Antagonism Induces Protection from Lethal Sepsis: Involvement of Toll-like Receptor 4 Signaling(2012) PETRONILHO, Fabricia; VUOLO, Francieli; GALANT, Leticia Selinger; CONSTANTINO, Larissa; TOMASI, Cristiane Damiani; GIOMBELLI, Vinicius Renne; SOUZA, Cldudio Teodoro de; SILVA, Sabrina da; BARBEIRO, Denise Frediani; SORIANO, Francisco Garcia; STRECK, Emilio Luiz; RITTER, Cristiane; ZANOTTO-FILHO, Alfeu; PASQUALI, Matheus Augusto; GELAIN, Daniel Pens; RYBARCZYK-FILHO, Jose Luiz; MOREIRA, Jose Claudio Fonseca; BLOCK, Norman L.; ROESLER, Rafael; SCHWARTSMANN, Gilberto; SCHALLY, Andrew V.; DAL-PIZZOL, FelipeIn sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha and RC-3095 (10 ng/mL), Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis. GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal-related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-kappa B and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-alpha. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00083
- Diazoxide reduces local and remote organ damage in a rat model of intestinal ischemia reperfusion(2018) DOURADO, Saulo Fernandes de Mattos; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; BARBEIRO, Hermes Vieira; SILVA, Fabiano Pinheiro da; MACHADO, Marcel Cerqueira CesarBackground: Intestinal ischemia reperfusion is a common clinical condition that causes functional impairment. Once tight junctions are damaged, barrier function is compromised, and the intestines become a source for entry of bacterial and inflammatory mediators into the circulation, leading to systemic inflammatory response syndrome, multiple organ failure, and death. It is possible that diazoxide could protect the intestines against ischemia reperfusion. The aim of this study is to determine whether diazoxide can provide protection in a rat model of intestinal ischemia reperfusion. Methods: A total of 32 adult male specific pathogen-free Wistar rats were randomized into three groups: a control group, n = 6; a saline group, n = 13; and a diazoxide group, n = 13. The saline and diazoxide groups underwent clamping of the superior mesenteric artery for 1 h, with samples in all the groups being collected 12 h later. Results: Intestinal histology showed greater damage in the intestinal ischemia reperfusion groups. mRNA expression of zonula occludens-1 and occludin (tight junction proteins) and interleukin-6 and cyclooxygenase-2 was the highest in the Saline group. The Diazoxide group showed a reduction in aspartate aminotransferase serum levels compared with the other groups. Conclusions: Increased expression of zonula occludens-1, occludin, and cyclooxygenase-2 suggested a greater regenerative effort because ofmore severe lesions in the saline group. In addition, increased expression of interleukin-6 in the saline group was suggestive of inflammation, indicating that diazoxide had protective effects in the diazoxide group. Reduced aspartate aminotransferase in the diazoxide group suggested liver protection. Diazoxide protects the intestines and liver fromintestinal ischemia reperfusion lesions in rats.
- High-fat diet inhibits PGC-1 alpha suppressive effect on NF kappa B signaling in hepatocytes(2018) BARROSO, Wermerson Assuncao; VICTORINO, Vanessa Jacob; JEREMIAS, Isabela Casagrande; PETRONI, Ricardo Costa; ARIGA, Suely Kunimi Kubo; SALLES, Thiago A.; BARBEIRO, Denise Frediani; LIMA, Thais Martins de; SOUZA, Heraldo Possolo deThe peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) regulates the expression of genes implicated in fatty acid oxidation and oxidative phosphorylation. Its role in liver steatosis is well established, since mice with liver-specific deletion of PGC-1 alpha exhibit lipid accumulation and high-fat diet reduces hepatic PGC-1 alpha expression in mice. In this study, we investigated the role of PGC-1 alpha in the inflammatory changes observed in steatohepatitis induced by high-fat diet. C57black/6 mice were fed a high-fat diet containing 30% fat for 10 weeks. After euthanasia, liver morphology was examined by HE staining and inflammation was determined by IL-6, TNF-alpha, and IL-1 beta quantification. Liver gene expression of PGC-1 isoforms was evaluated by real-time PCR and p65 NF kappa B nuclear translocation by Western blotting. HepG2 cells were treated with linoleic acid overload for 72 h to create an in vitro model of steatohepatitis. RNA interference (RNAi) was used to evaluate the involvement of PGC-1 alpha on inflammatory mediators' production by hepatocytes. The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. Mice liver also exhibited increased proinflammatory cytokines' levels, decreased PGC-1 alpha expression, and marked increase in p65 NF kappa B nuclear translocation. Linoleic acid treated cells also presented increased expression of proinflammatory cytokines and decreased PGC-1 alpha expression. The knockdown of PGC-1 alpha content caused an increase in IL-6 expression and release via enhanced I kappa B alpha phosphorylation and subsequent increase of p65 NF kappa B nuclear translocation. High-fat diet induces liver inflammation by inhibiting PGC-1 alpha expression and its suppressive effect in NF kappa B pathway.
- Hypertonic saline solution reduces the inflammatory response in endotoxemic rats(2012) THEOBALDO, Mariana Cardillo; BARBEIRO, Hermes Vieira; BARBEIRO, Denise Frediani; PETRONI, Ricardo; SORIANO, Francisco GarciaOBJECTIVE: Volume replacement in septic patients improves hemodynamic stability. This effect can reduce the inflammatory response. The objective of this study was to evaluate the effect of 7.5% hypertonic saline solution versus 0.9% normal saline solution for volume replacement during an inflammatory response in endotoxemic rats. METHODS: We measured cytokines (serum and gut), nitrite, and lipid peroxidation (TBARS) as indicators of oxidative stress in the gut. Rats were divided into four groups: control group (C) that did not receive lipopolysaccharide; lipopolysaccharide injection without treatment (LPS); lipopolysaccharide injection with saline treatment (LPS + S); and lipopolysaccharide injection with hypertonic saline treatment (LPS + H). Serum and intestine were collected. Measurements were taken at 1.5, 8, and 24 h after lipopolysaccharide administration. RESULTS: Of the four groups, the LPS + H group had the highest survival rate. Hypertonic saline solution treatment led to lower levels of IL-6, IL-10, nitric oxide, and thiobarbituric acid reactive substances compared to 0.9% normal saline. In addition, hypertonic saline treatment resulted in a lower mortality compared to 0.9% normal saline treatment in endotoxemic rats. Volume replacement reduced levels of inflammatory mediators in the plasma and gut. CONCLUSION: Hypertonic saline treatment reduced mortality and lowered levels of inflammatory mediators in endotoxemic rats. Hypertonic saline also has the advantage of requiring less volume replacement.
- Cytokine and chemokine levels in the heart tissue of aged rats following severe acute pancreatitis(2017) AMARAL, Rizia Callou; BARBEIRO, Denise Frediani; KOIKE, Marcia Kiyomi; MADY, Charles; MACHADO, Marcel Cerqueira Cesar; SILVA, Fabiano Pinheiro daSevere acute pancreatitis (AP) is a disease associated with high mortality and characterized by overwhelming systemic inflammation. Older people have a prolonged hospital stay and worst prognosis, when affected by this disease. Our group hypothesized, thus, that the systemic inflammatory response in the elderly would promote more organ damage when compared to the young. We sought to investigate the effect of systemic inflammation on the gene expression of cytokines, chemokines, and growth factors in the hearts of older and younger rats in an animal model of AP. AP was induced in all rats by injection of 0.5 mL of 2.5% taurocholate. There were two healthy age-matched control groups. An array of 79 cytokines, chemokines, and growth factors was measured in samples of cardiac tissue taken from the AP rats after 10 h, and from control rats. Older healthy rats had significantly higher levels of interleukin-10 (IL-10) and CCL1 gene expression than younger ones (P < 0.05), but all other measurements were similar among the study groups. This study indicates the systemic inflammation may show unique features for different organs in the body, but older animals with systemic inflammation are similar to the young regarding the cardiac inflammatory response.
- Collagen V alpha 1 Chain Decrease in Papillary Dermis from Early Systemic Sclerosis: A New Proposal in Cutaneous Fibrosis Molecular Structure(2022) MORAIS, Jymenez de; VELOSA, Ana Paula P.; ANDRADE, Priscila C.; FREDIANI, Denise; CARRASCO, Solange; QUEIROZ, Zelita A. de Jesus; MARTIN, Patricia; SAITO, Renata F.; ELIAS, Vitoria; GOLDENSTEIN-SCHAINBERG, Claudia; CHAMMAS, Roger; SAMPAIO-BARROS, Percival D.; CAPELOZZI, Vera L.; TEODORO, Walcy R.Cutaneous fibrosis is one of the main features of systemic sclerosis (SSc). Recent findings correlated abnormal collagen V (Col V) deposition in dermis with skin thickening and disease activity in SSc. Considering that Col V is an important regulator of collagen fibrillogenesis, understanding the role of Col V in the first two years of the skin fibrosis in SSc (early SSc) can help to determine new targets for future treatments. In this study, we analyzed the morphological, ultrastructural and molecular features of alpha 1(V) and alpha 2(V) chains and the expression of their coding genes COL5A1 and COL5A2 in collagen fibrillogenesis in early-SSc. Skin biopsies were obtained from seven consecutive treatment-naive patients with SSc-related fibrosis and four healthy controls. Our data showed increased alpha 1(V) and alpha 2(V) chain expression in the reticular dermis of early-SSc patients; however, immunofluorescence and ultrastructural immunogold staining determined a significant decreased expression of the alpha 1(V) chain along the dermoepidermal junction in the papillary dermis from early-SSc-patients in relation to the control (12.77 +/- 1.34 vs. 66.84 +/- 3.36; p < 0.0001). The immunoblot confirmed the decreased expression of the alpha 1(V) chain by the cutaneous fibroblasts of early-SSc, despite the increased COL5A1 and COL5A2 gene expression. In contrast, the alpha 2(V) chain was overexpressed in the small vessels (63.18 +/- 3.56 vs. 12.16 +/- 0.81; p < 0.0001) and capillaries (60.88 +/- 5.82 vs. 15.11 +/- 3.80; p < 0.0001) in the reticular dermis of early-SSc patients. Furthermore, COLVA2 siRNA in SSc cutaneous fibroblasts resulted in a decreased alpha 1(V) chain expression. These results highlight an intense decrease in the alpha 1(V) chain along the dermoepidermal junction, suggesting an altered molecular histoarchitecture in the SSc papillary dermis, with a possible decrease in the expression of the alpha 1(V)3 homotrimeric isoform, which could interfere with the thickening and cutaneous fibrosis related to SSc.
- Cathelicidin LL-37 bloodstream surveillance is down regulated during septic shock(2013) BARBEIRO, Denise Frediani; BARBEIRO, Hermes Vieira; ZAMPIERI, Fernando Godinho; MACHADO, Marcel Cerqueira Cesar; TORGGLER FILHO, Francisco; CUNHA, Debora Maria Gomes; GOULART, Alessandra Carvalho; VELASCO, Irineu Tadeu; CRUZ NETO, Luiz Monteiro da; SOUZA, Heraldo Possolo de; SILVA, Fabiano Pinheiro daHost defense peptides are ancient weapons of the innate immunity. The human cathelicidin LL-37 protects the epithelial barrier against infection and is constitutively secreted in the bloodstream by immune cells. Current knowledge claims that LL-37 is up regulated upon infection. LL-37 can protect against bacterial infections and possesses many immunomodulatory properties. Here, we show that the human host defense peptide LL-37 is down regulated during septic shock. Furthermore, we show that these effects are not related to vitamin D serum levels, a potent inducer of LL-37 gene expression, pointing out the complex regulation of cathelicidins during septic shock.
- Interleukin-15 and Interleukin-7 are the Major Cytokines to Maintain Endometriosis(2019) BELLELIS, Patrick; BARBEIRO, Denise Frediani; GUEUVOGHLANIAN-SILVA, Barbara Yasmin; KALIL, Jorge; ABRAO, Mauricio Simoes; PODGAEC, SergioObjective: The objective of this study was to evaluate cytokines related to natural killer and T-regulatory cells in endometriotic lesions, peritoneal fluid (PF) and the peripheral blood (PB) of patients with deep infiltrative endometriosis. Study Design: A case-control study was conducted in a tertiary referral hospital. Sixty-four consecutive patients after laparoscopy were divided into 2 groups: with endometriosis (Group A - n = 32) and without endometriosis (Group B - n = 32). Main Outcome Measures: Interleukin (IL)-2, IL-4, IL-7, IL-10, IL-12, IL-15, transforming growth factor beta 1, and IFN gamma concentration was measured using a Luminex(TM) multiplex suspension bead array. Tissues from endometriotic lesions of patients with endometriosis and from eutopic endometrium were evaluated, as well as PF and PB of all patients. Results: Compared to the other analyzed groups, IL-15 concentration was significantly higher in the ectopic endometrium and IL-7 in the eutopic endometrium of the endometriosis group (p < 0.05). Compared to endometriosis group, IFN gamma, IL-7, and IL-15 were observed to be significantly higher in the PF of the control group, and IL-10 was lower in the control group (p < 0.05). In PB, compared to endometriosis group, IL-4, IL-10, IL-12, IL-15, and IFN gamma concentrations were significantly higher in the control group (p < 0.05). Conclusions: Our hypothesis is that deep endometriosis is a disease out of control. This disease's nature is of progression and invasion of adjacent structures, and proof of this disease state is the disorganized secretion of cytokine regulation and inflammation, which seem to be among the factors responsible for the maintenance of the disease.
- Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease(2018) GUEUVOGHLANIAN-SILVA, Barbara Yasmin; BELLELIS, Patrick; BARBEIRO, Denise Frediani; HERNANDES, Camila; PODGAEC, SergioThe aim of this study was to evaluate Treg and NK cells related cytokines in deep infiltrating endometriosis lesions and its relationship with clinical symptoms of the disease. mRNA expression of Transforming Growth Factor Beta (TGFB), Interleukin (IL)10, Interferon Gamma (IFNG), IL7, and IL15 was analyzed by Real-Time PCR in eutopic endometrium and rectosigmoid lesions from 11 women with deep infiltrating endometriosis and in eutopic endometrium from 11 healthy women. IL10, IFNG, and IL7 expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from women with endometriosis. IL10 and TGFB expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from healthy women. In addition, TGFB and IL15 levels correlated positively with deep dyspareunia and cyclic dyschezia, respectively, while IL7 levels correlated negatively with dysmenorrhea. Deep infiltrating rectosigmoid endometriosis displays alterations in Treg and NK cells related cytokine, and TGFB, IL7 and IL15 expression is related with dyspareunia, dysmenorrhea and cyclic dyschezia, respectively, in patients with the disease.