Lirlândia P Sousa

Federal University of Minas Gerais, Cidade de Minas, Minas Gerais, Brazil

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Publications (47)203.51 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphatidylinositol 3-kinase (PI3K) is an enzyme involved in different pathophysiological processes, including neurological disorders. However, its role in seizures and postictal outcomes is still not fully understood. We investigated the role of PI3Kγ on seizures, production of neurotrophic and inflammatory mediators, expression of a marker for microglia, neuronal death and hippocampal neurogenesis in mice (WT and PI3Kγ(-/-)) subjected to intrahippocampal microinjection of pilocarpine. PI3Kγ(-/-) mice presented a more severe status epilepticus (SE) than WT mice. In hippocampal synaptosomes, genetic or pharmacological blockade of PI3Kγ enhanced the release of glutamate and the cytosolic calcium concentration induced by KCl. There was an enhanced neuronal death and a decrease in the doublecortin positive cells in the dentate gyrus of PI3Kγ(-/-) animals after the induction of SE. Levels of BDNF were significantly increased in the hippocampus of WT and PI3Kγ(-/-) mice, although in the prefrontal cortex, only PI3Kγ(-/-) animals showed significant increase in the levels of this neurotrophic factor. Pilocarpine increased hippocampal microglial immunolabeling in both groups, albeit in the prelimbic, medial and motor regions of the prefrontal cortex this increase was observed only in PI3Kγ(-/-) mice. Regarding the levels of inflammatory mediators, pilocarpine injection increased interleukin (IL) 6 in the hippocampus of WT and PI3Kγ(-/-) animals and in the prefrontal cortex of PI3Kγ(-/-) animals 24 hours (h) after the stimulus. Levels of TNFα were enhanced in the hippocampus and prefrontal cortex of only PI3Kγ(-/-) mice at this time point. On the other hand, PI3Kγ deletion impaired the increase in IL-10 in the hippocampus induced by pilocarpine. In conclusion, the lack of PI3Kγ revealed a deleterious effect in an animal model of convulsions induced by pilocarpine, suggesting that this enzyme may play a protective role in seizures and pathological outcomes associated with this condition. Copyright © 2015. Published by Elsevier Inc.
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    ABSTRACT: Eosinophils are effector cells that have an important role in the pathogenesis of allergic disease. Defective removal of these cells likely leads to chronic inflammatory diseases such as asthma. Thus, there is great interest in understanding the mechanisms responsible for the elimination of eosinophils from inflammatory sites. Previous studies have demonstrated a role for certain mediators and molecular pathways responsible for the survival and death of leukocytes at sites of inflammation. Reactive oxygen species have been described as proinflammatory mediators but their role in the resolution phase of inflammation is poorly understood. The aim of this study was to investigate the effect of reactive oxygen species in the resolution of allergic inflammatory responses. An eosinophilic cell line (Eol-1) was treated with hydrogen peroxide and apoptosis was measured. Allergic inflammation was induced in ovalbumin sensitized and challenged mouse models and reactive oxygen species were administered at the peak of inflammatory cell infiltrate. Inflammatory cell numbers, cytokine and chemokine levels, mucus production, inflammatory cell apoptosis and peribronchiolar matrix deposition was quantified in the lungs. Resistance and elastance were measured at baseline and after aerosolized methacholine. Hydrogen peroxide accelerates resolution of airway inflammation by induction of caspase-dependent apoptosis of eosinophils and decrease remodeling, mucus deposition, inflammatory cytokine production and airway hyperreactivity. Moreover, the inhibition of reactive oxygen species production by apocynin or in gp91(phox-/-) mice prolonged the inflammatory response. Hydrogen peroxide induces Eol-1 apoptosis in vitro and enhances the resolution of inflammation and improves lung function in vivo by inducing caspase-dependent apoptosis of eosinophils.
    Cell Death & Disease 02/2015; x(x):x. DOI:10.1038/cddis.2014.580 · 5.18 Impact Factor
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    ABSTRACT: The plasminogen (Plg)/plasmin (Pla) system is associated with a variety of biological activities beyond the classical dissolution of fibrin clots, including cell migration, tissue repair, and inflammation. Although the capacity of Plg/Pla to induce cell migration is well defined, the mechanism underlying this process in vivo is elusive. In this study, we show that Pla induces in vitro migration of murine fibroblasts and macrophages (RAW 264.7) dependent on the MEK/ERK pathway and by requiring its proteolytic activity and lysine binding sites. Plasmin injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that was associated with augmented ERK1/2 and IκB-α phosphorylation and increased levels of CCL2 and IL-6 in pleural exudates. The inhibition of protease activity by using a serine protease inhibitor leupeptin or two structurally different protease-activated receptor-1 antagonists (SCH79797 and RWJ56110) abolished Pla-induced mononuclear recruitment and ERK1/2 and IκB-α phosphorylation. Interestingly, inhibition of the MEK/ERK pathway abolished Pla-induced CCL2 upregulation and mononuclear cell influx. In agreement with a requirement for the CCL2/CCR2 axis to Pla-induced cell migration, the use of a CCR2 antagonist (RS504393) prevented the Plg/Pla-induced recruitment of mononuclear cells to the pleural cavity and migration of macrophages at transwell plates. Therefore, Pla-induced mononuclear cell recruitment in vivo was dependent on protease-activated receptor-1 activation of the MEK/ERK/NF-κB pathway, which led to the release of CCL2 and activation of CCR2.
    The Journal of Immunology 08/2014; 193(7). DOI:10.4049/jimmunol.1400334 · 5.36 Impact Factor
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    ABSTRACT: Inflammation is a physiological response of the immune system to injury or infection but may become chronic. In general, inflammation is self-limiting and resolves by activating a termination program named resolution of inflammation. It has been argued that unresolved inflammation may be the basis of a variety of chronic inflammatory diseases. Resolution of inflammation is an active process that is fine-tuned by the production of proresolving mediators and the shutdown of intracellular signaling molecules associated with cytokine production and leukocyte survival. Apoptosis of leukocytes (especially granulocytes) is a key element in the resolution of inflammation and several signaling molecules are thought to be involved in this process. Here, we explore key signaling molecules and some mediators that are crucial regulators of leukocyte survival in vivo and that may be targeted for therapeutic purposes in the context of chronic inflammatory diseases.
    Mediators of Inflammation 07/2014; 2014:829851. DOI:10.1155/2014/829851 · 2.42 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Clinica Chimica Acta 06/2014; 436. DOI:10.1016/j.cca.2014.05.027 · 2.76 Impact Factor
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    ABSTRACT: Background: Despite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-beta 1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE. Methods: Plasma levels of sEng, TGF-beta 1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity [mild (n = 12) and severe (n = 31)] and onset-time of the disease [ early (n = 19) and late (n = 24)]. Results: Pregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-beta 1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-beta 1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-beta 1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity. Conclusions: These results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation.
    PLoS ONE 05/2014; 9(5):e97632. DOI:10.1371/journal.pone.0097632 · 3.53 Impact Factor
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    ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Neurotrophic factors and inflammatory markers may play considerable roles in AD. In this study we measured, through Enzyme-Linked Immunosorbent Assay, the plasma levels of brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and neuronal growth factor (NGF), as well as tumor necrosis factor-alpha soluble receptors, sTNFR1 and sTNFR2, and soluble intercellular adhesion molecule 1 (sICAM-1), in 50 AD patients, 37 patients with mild cognitive impairment (MCI) and 56 healthy elderly controls. BDNF levels, expressed as median and interquartile range, were higher for AD patients (2545.3, 1497.4-4153.4 pg/ml) compared to controls (1503.8, 802.3-2378.4 pg/ml), P < 0.001. sICAM-1 was also higher in AD patients. sTNFR1 levels were increased in AD when compared to controls and also to MCI. GDNF, NGF and sTNFR2 levels showed no significant differences among the studied groups. The increase in BDNF might reflect a compensatory mechanism against early neurodegeneration and seems to be related to inflammation. sTNFR1 appears to mark not only the inflammatory state but also differentiates between MCI and AD, which may be an additional tool for differentiating degrees of cognitive impairment.
    Journal of Psychiatric Research 02/2014; DOI:10.1016/j.jpsychires.2014.01.019 · 4.09 Impact Factor
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    ABSTRACT: Bipolar disorder (BD) is a severe psychiatric disorder of complex physiopathology that has been associated with a pro-inflammatory state. The aim of the present study was to investigate intracellular pathways associated with inflammatory signaling, assessing the phosphorylation levels of transcription factor nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) in peripheral blood mononuclear cells of euthymic BD patients and healthy controls. Fifteen BD euthymic type I patients, and 12 healthy controls matched by age and gender were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients also by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Phosphorylation levels of p65 NF-κB subunit, and MAPK ERK1/2, and p38 were assessed by Western blot and flow cytometry. Plasma cytokines (IL-2, IL-4, IL6, IL-10, IFN-γ, TNF-α, and IL-17A) were measured using cytometric bead arrays. Western blot and flow cytometry analyses showed increased phosphorylation levels of p65 NF-κB subunit, and MAPKs ERK1/2, and p38 in BD patients in euthymia in comparison with controls. BD patients presented increased pro-inflammatory cytokines levels in comparison with controls, and TNF-α correlated with the levels of phosphorylated p65 NF-κB. The present study found increased activation of MAPK and NF-κB pathways in BD patients, which is in line with a pro-inflammatory status.
    Journal of Psychiatric Research 09/2013; DOI:10.1016/j.jpsychires.2013.08.019 · 4.09 Impact Factor
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    ABSTRACT: Preeclampsia (PE) is a syndrome characterized by poor placentation and endothelial dysfunction. The diagnosis for this syndrome is based in hypertension and proteinuria presented after the 20th week of pregnancy. Despite intensive research, PE is still one of the leading causes of maternal mortality, although reliable screening tests or effective treatments of this disease have yet to be proposed. Microparticles (MPs) are small vesicles released after cell activation or apoptosis, which contain membrane proteins that are characteristic of the original parent cell. MPs have been proven to play key role in thrombosis, inflammation, and angiogenesis, as well as to mediate cell-cell communication by transferring mRNAs and microRNA from the cell of origin to target cells. Placenta-derived syncytiotrophoblast MPs are one of the most increased MPs during PE and may play an important role in the pathogenesis of this syndrome. Therefore, a better overall understanding of the role of MPs in PE may be useful for new clinical diagnoses and therapeutic approaches.
    Molecular Biology Reports 05/2013; DOI:10.1007/s11033-013-2536-0 · 1.96 Impact Factor
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    ABSTRACT: Inflammation is a beneficial host reaction to tissue damage and has the essential primary purpose of restoring tissue homeostasis. Inflammation plays a major role in containing and resolving infection and may also occur under sterile conditions. The cardinal signs of inflammation dolor, calor, tumor and rubor are intrinsically associated with events including vasodilatation, edema and leukocyte trafficking into the site of inflammation. If uncontrolled or unresolved, inflammation itself can lead to further tissue damage and give rise to chronic inflammatory diseases and autoimmunity with eventual loss of organ function. It is now evident that the resolution of inflammation is an active continuous process that occurs during an acute inflammatory episode. Successful resolution requires activation of endogenous programs with switch from production of pro-inflammatory towards pro-resolving molecules, such as specific lipid mediators and annexin A1, and the non-phlogistic elimination of granulocytes by apoptosis with subsequent removal by surrounding macrophages. These processes ensure rapid restoration of tissue homeostasis. Here, we review recent advances in the understanding of resolution of inflammation, highlighting the pharmacological strategies that may interfere with the molecular pathways which control leukocyte survival and clearance. Such strategies have proved beneficial in several pre-clinical models of inflammatory diseases, suggesting that pharmacological modulation of the resolution process may be useful for the treatment of chronic inflammatory diseases in humans.
    Pharmacology [?] Therapeutics 04/2013; DOI:10.1016/j.pharmthera.2013.04.006 · 7.75 Impact Factor
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    ABSTRACT: The inflammatory response is a physiological process that has the major role of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation may cause tissue damage and contribute to the pathogenesis of chronic inflammatory and autoimmune diseases. Current pharmacological therapies to treat inflammatory maladies focus on inhibition of the productive phase of the inflammatory response including inhibition of leukocyte influx. Resolution of inflammation is an active process, which relies on the production of pro-resolving molecules and activation of intracellular pathways. Here, we will discuss mechanisms and therapeutic potential of pharmacological strategies, which accelerate resolution in animal models of acute inflammation by mimicking or inducing natural pathways of resolution phase of inflammation.
    Current Opinion in Pharmacology 04/2013; DOI:10.1016/j.coph.2013.03.007 · 4.23 Impact Factor
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    ABSTRACT: Growing evidences suggest that Saccharomyces boulardii (SB) is efficacious against bacterial infections and inflammatory bowel diseases. This study investigated the effects of treatment with SB provided in a murine model of typhoid fever. Mice were divided into two groups: (1) control animals challenged with Salmonella Typhimurium (ST), and (2) animals receiving SB, and then challenged with ST. At days 0, 1, 5, 10 and 15 post-challenge, animals were euthanized and tissues collected to analyze bacterial translocation, cytokines, signaling pathways and histological analysis. Survival rate and animal weight were also evaluated. Treatment with SB increased survival rate and inhibited translocation of bacteria after ST challenge. Histological data showed that SB also protected mice against liver damage induced by ST. SB decreased levels of inflammatory cytokines and activation of mitogen-activated protein kinases (p38, JNK and ERK1/2), phospho-IκB, p65-RelA, phospho-jun and c-fos in the colon, signal pathways involved in the activation of inflammation induced by ST. Further experiments revealed that probiotic effects were due, at least in part, to the binding of ST to the yeast. Such binding diminishes ST translocation, resulting in decreased activation of signaling pathways which lead to intestinal inflammation in a murine model of typhoid fever.
    Microbes and Infection 01/2013; DOI:10.1016/j.micinf.2012.12.007 · 2.73 Impact Factor
  • Thrombosis Research 01/2013; 131:S88. DOI:10.1016/S0049-3848(13)70091-4 · 2.43 Impact Factor
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    ABSTRACT: The Type 2 diabetes mellitus (DM2) is considered nowadays as one of the most important chronic disturbances because of the significant number of people with diabetes and its severe complications, responsible for elevated indexes of morbidity and mortality. DM2 is characterized by several degrees of insulin resistance and relative deficiency in its secretion. Genetic and environmental factors have been described as of major importance in the DM2 development as obesity, which is directly correlated with development of resistance in peripheral tissues and inflammatory state in metabolic activated adipose tissue. Inflammatory responses may have a dual role in DM2, since it may have either a causal relationship leading to resistance to insulin or may be intensified by the hyperglycemic state, resulting in DM2 complications. In this review, we discuss the association of polymorphisms in genes encoding inflammatory cytokines and the increased level of these pro-inflammatory markers, associated to chronic pathologic conditions in DM2.
    Diabetes research and clinical practice 12/2012; 99(2). DOI:10.1016/j.diabres.2012.09.003 · 2.74 Impact Factor
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    ABSTRACT: BACKGROUND: There may be a relationship between endothelial dysfunction, coagulation activation and nitric oxide (NO) synthesis in women with mild and severe preeclampsia (PE). METHODS: Plasma thrombomodulin (TM), D-Dimer (D-Di), cyclic guanosine monophosphate (cGMP) and placental nitric oxide synthase activity (NOS) were investigated in 21 normotensive pregnant women (G1), 22 pregnant women with mild PE (G2) and 20 pregnant women with severe PE (G3). RESULTS: TM and D-Di were significantly increased in G3 compared to G1 (P=0.001 and P=0.006, respectively) and G2 (P=0.001, in both cases). However, there was no significant difference when G1 was compared to G2. For total NOS, calcium independent NOS, calcium dependent NOS no significant difference was observed among the groups studied. CONCLUSIONS: TM and D-Di levels are raised in women with severe PE compared to normotensive pregnant women and women with mild PE. While increased TM levels may reflect endothelial dysfunction, raised D-Di levels indicate a hypercoagulable state. NO assessed by 2 indirect methods did not show any significant difference among the groups studied. Due to current limitations with in vitro NO measurements and interferences associated with NO bioavailability, particularly in PE, such findings should not be over-interpreted.
    Clinica chimica acta; international journal of clinical chemistry 10/2012; 415. DOI:10.1016/j.cca.2012.10.006 · 2.54 Impact Factor
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    ABSTRACT: Background: Bipolar disorder (BD) is a severe psychiatric disorder of unknown physiopathology that has been associated with a proinflammatory state. The aim of the present study was to compare the phosphorylation levels of the signaling proteins involved with induction of proinflammatory mediators, such as mitogen-activated protein kinase (MAPKs) and the transcription factor nuclear factor Kappa B (NF-kappa B), in peripheral blood mononuclear cell of euthymic BD patients and control subjects. Methods: 15 BD euthymic type I patients, and 16 healthy controls matched by age and gender were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. Phosphorylation of ERK1/2, and p38-MAPK were assessed by Western blot and flow cytometry. The expression of NF-kappa B p65/RelA was estimated by the mean fluorescence intensity evaluated by flow cytometry. Results: Western blot analysis showed increased phosphorylation levels of p38-MAPK (p < 0.001) and ERK1/2 (p = 0.003) in BD patients when compared to controls. BD patients showed increased expression of NF-kappa B p65/RelA, as estimated by the mean fluorescence intensity (p = 0.01). Conclusion: The present study found altered activation of MAPK and NF-kappa B pathway BD patients which is in line with the illness proinflammatory status.
    Brain Behavior and Immunity 09/2012; 26:S35. DOI:10.1016/j.bbi.2012.07.150 · 6.13 Impact Factor
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    ABSTRACT: There are few animal models of dengue infection, especially in immunocompetent mice. Here, we describe alterations found in adult immunocompetent mice inoculated with an adapted Dengue virus (DENV-3) strain. Infection of mice with the adapted DENV-3 caused inoculum-dependent lethality that was preceded by several hematological and biochemical changes and increased virus dissemination, features consistent with severe disease manifestation in humans. IFN-γ expression increased after DENV-3 infection of WT mice and this was preceded by increase in expression of IL-12 and IL-18. In DENV-3-inoculated IFN-γ(-/-) mice, there was enhanced lethality, which was preceded by severe disease manifestation and virus replication. Lack of IFN-γ production was associated with diminished NO-synthase 2 (NOS2) expression and higher susceptibility of NOS2(-/-) mice to DENV-3 infection. Therefore, mechanisms of protection to DENV-3 infection rely on IFN-γ-NOS2-NO-dependent control of viral replication and of disease severity, a pathway showed to be relevant for resistance to DENV infection in other experimental and clinical settings. Thus, the model of DENV-3 infection in immunocompetent mice described here represents a significant advance in animal models of severe dengue disease and may provide an important tool to the elucidation of immunopathogenesis of disease and of protective mechanisms associated with infection.
    PLoS Neglected Tropical Diseases 05/2012; 6(5):e1663. DOI:10.1371/journal.pntd.0001663 · 4.49 Impact Factor
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    ABSTRACT: This study aimed at assessing whether AnxA1, a downstream mediator for the anti-inflammatory effects of GCs, could affect the fate of immune cells in tissue exudates, using LPS-induced pleurisy in BALB/c mice. AnxA1 protein expression in exudates was increased during natural resolution, as seen at 48-72 h post-LPS, an effect augmented by treatment with GC and associated with marked presence of apoptotic neutrophils in the pleural exudates. The functional relevance of AnxA1 was determined using a neutralizing antibody or a nonspecific antagonist at FPR/ALXRs: either treatment inhibited both spontaneous and GC-induced resolution of inflammation. Injection of Ac2-26 (100 μg, given 4 h into the LPS response), an AnxA1-active N-terminal peptide, promoted active resolution and augmented the extent of neutrophil apoptosis. Such an effect was prevented by the pan-caspase inhibitor zVAD-fmk. Mechanistically, resolution of neutrophilic inflammation was linked to cell apoptosis with activation of Bax and caspase-3 and inhibition of survival pathways Mcl-1, ERK1/2, and NF-κB. These novel in vivo data, using a dynamic model of acute inflammation, provide evidence that AnxA1 is a mediator of natural and GC-induced resolution of inflammation with profound effects on neutrophil apoptosis.
    Journal of leukocyte biology 04/2012; 92(2):249-58. DOI:10.1189/jlb.0112008 · 4.99 Impact Factor
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    ABSTRACT: We aimed to determine the plasma levels of cytokines in patients with obsessive-compulsive disorder (OCD) as compared with healthy controls and to investigate whether there is any association between their concentrations and OCD clinical and therapeutic features. Forty patients with OCD and 40 healthy controls had their plasmas assessed for a range of cytokines (tumor necrosis factor-α, or TNF-α), chemokines (CCL2, CCL3, CCL11, CCL24, CXCL8, CXCL9, CXCL10), and other mediators (TNF soluble receptors sTNFR1 and sTNFR2 and interleukin-1 receptor antagonist) by enzyme-linked immunosorbent assay. Patients with OCD were further examined with the Mini-International Neuropsychiatric Interview, the Obsessive-Compulsive Inventory-Revised, and the Beck Depression Inventory. Compared with healthy controls, patients with OCD exhibited significantly increased plasma levels of CCL3, CXCL8, sTNFR1, and sTNFR2. Among patients with OCD, there was a positive correlation between relative antidepressant dose and sTNFr2 levels. Furthermore, although the levels of sTNFR1 correlated positively with the severity of washing symptoms, CCL24 levels correlated negatively with the severity of hoarding. The levels of certain immune markers are increased in adult patients with OCD and seem to vary according to predominant symptoms dimensions. Other studies are required to establish whether our findings truly reflect immunologic dysfunction in OCD or are the result of other hidden confounding factors.
    Comprehensive psychiatry 01/2012; 53(6):797-804. DOI:10.1016/j.comppsych.2011.12.007 · 2.08 Impact Factor
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    ABSTRACT: Dengue is a mosquito-borne disease caused by one of four serotypes of Dengue virus (DENV-1-4). Severe dengue infection in humans is characterized by thrombocytopenia, increased vascular permeability, hemorrhage and shock. However, there is little information about host response to DENV infection. Here, mechanisms accounting for IFN-γ production and effector function during dengue disease were investigated in a murine model of DENV-2 infection. IFN-γ expression was greatly increased after infection of mice and its production was preceded by increase in IL-12 and IL-18 levels. In IFN-γ(-/-) mice, DENV-2-associated lethality, viral loads, thrombocytopenia, hemoconcentration, and liver injury were enhanced, when compared with wild type-infected mice. IL-12p40(-/-) and IL-18(-/-) infected-mice showed decreased IFN-γ production, which was accompanied by increased disease severity, higher viral loads and enhanced lethality. Blockade of IL-18 in infected IL-12p40(-/-) mice resulted in complete inhibition of IFN-γ production, greater DENV-2 replication, and enhanced disease manifestation, resembling the response seen in DENV-2-infected IFN-γ(-/-) mice. Reduced IFN-γ production was associated with diminished Nitric Oxide-synthase 2 (NOS2) expression and NOS2(-/-) mice had elevated lethality, more severe disease evolution and increased viral load after DENV-2 infection. Therefore, IL-12/IL-18-induced IFN-γ production and consequent NOS2 induction are of major importance to host resistance against DENV infection.
    PLoS Neglected Tropical Diseases 12/2011; 5(12):e1449. DOI:10.1371/journal.pntd.0001449 · 4.49 Impact Factor

Publication Stats

884 Citations
203.51 Total Impact Points


  • 2001–2015
    • Federal University of Minas Gerais
      • • Faculty of Pharmacy
      • • Institute of Biological Sciences
      • • Departamento de Análises Clínicas e Toxicológicas
      • • Departamento de Bioquímica e Imunologia
      • • Departamento de Microbiologia
      Cidade de Minas, Minas Gerais, Brazil
  • 2010–2013
    • The University of Edinburgh
      • Queen's Medical Research Institute
      Edinburgh, SCT, United Kingdom
    • Max-Delbrück-Centrum für Molekulare Medizin
      Berlín, Berlin, Germany