ORCID Profile
0000-0002-1042-9762
Current Organisation
Universidade Federal de Minas Gerais
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Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.COMPPSYCH.2011.12.007
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.
Publisher: The American Association of Immunologists
Date: 15-05-2015
Abstract: Glucocorticoid (GC)-induced leucine zipper (GILZ) has been shown to mediate or mimic several actions of GC. This study assessed the role of GILZ in self-resolving and GC-induced resolution of neutrophilic inflammation induced by LPS in mice. GILZ expression was increased during the resolution phase of LPS-induced pleurisy, especially in macrophages with resolving phenotypes. Pretreating LPS-injected mice with trans-activator of transcription peptide (TAT)–GILZ, a cell-permeable GILZ fusion protein, shortened resolution intervals and improved resolution indices. Therapeutic administration of TAT-GILZ induced inflammation resolution, decreased cytokine levels, and promoted caspase-dependent neutrophil apoptosis. TAT-GILZ also modulated the activation of the survival-controlling proteins ERK1/2, NF-κB and Mcl-1. GILZ deficiency was associated with an early increase of annexin A1 (AnxA1) and did not modify the course of neutrophil influx induced by LPS. Dexamethasone treatment resolved inflammation and induced GILZ expression that was dependent on AnxA1. Dexamethasone-induced resolution was not altered in GILZ−/− mice due to compensatory expression and action of AnxA1. Our results show that therapeutic administration of GILZ efficiently induces a proapoptotic program that promotes resolution of neutrophilic inflammation induced by LPS. Alternatively, a lack of endogenous GILZ during the resolution of inflammation is compensated by AnxA1 overexpression.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.AJPATH.2011.09.038
Abstract: Cerebral malaria is a severe form of the disease that may result, in part, from an overt inflammatory response during infection by Plasmodium falciparum. The understanding of the pathogenesis of cerebral malaria may aid in the development of better therapeutic strategies for patients. The immune response in cerebral malaria involves elevation of circulating levels of cytokines and chemokines associated with leukocyte accumulation and breakdown of the blood-brain barrier in the central nervous system. Platelet-activating factor (PAF) is a mediator of inflammation shown to orchestrate inflammatory processes, including recruitment of leukocytes and increase of vascular permeability. Using mice lacking the PAF receptor (PAFR(-/-)), we investigated the relevance of this molecule for the outcome and the neuroinflammatory process triggered by P. berghei ANKA, an experimental model of cerebral malaria. In PAFR(-/-) mice, lethality was markedly delayed and brain inflammation was significantly reduced, as demonstrated by histology, accumulation, and activation of CD8(+) T cells, changes in vascular permeability and activation of caspase-3 on endothelial cells and leukocytes. Similarly, treatment with the PAFR antagonist UK-74,505 delayed lethality. Taken together, the results suggest that PAFR signaling is crucial for the development of experimental cerebral malaria. Mechanistically, PAFR activation is crucial for the cascade of events leading to changes in vascular permeability, accumulation, and activation of CD8(+) T cells and apoptosis of leukocytes and endothelial cells.
Publisher: Oxford University Press (OUP)
Date: 05-08-2016
DOI: 10.1189/JLB.3A1015-453RRR
Abstract: Gout is a disease characterized by the deposition of monosodium urate (MSU) crystals in the joints. Continuous gout episodes may lead to unresolved inflammatory responses and tissue damage. We investigated the effects of a high-fiber diet and acetate, a short-chain fatty acid (SCFA) resulting from the metabolism of fiber by gut microbiota, on the inflammatory response in an experimental model of gout in mice. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. The onset of inflammatory response induced by MSU crystals was not altered in animals given a high-fiber diet, but the high-fiber diet induced faster resolution of the inflammatory response. Similar results were obtained in animals given the SCFA acetate. Acetate was effective, even when given after injection of MSU crystals at the peak of the inflammatory response and induced caspase-dependent apoptosis of neutrophils that accounted for the resolution of inflammation. Resolution of neutrophilic inflammation was associated with decreased NF-κB activity and enhanced production of anti-inflammatory mediators, including IL-10, TGF-β, and annexin A1. Acetate treatment or intake of a high-fiber diet enhanced efferocytosis, an effect also observed in vitro with neutrophils treated with acetate. In conclusion, a high-fiber diet or one of its metabolic products, acetate, controls the inflammatory response to MSU crystals by favoring the resolution of the inflammatory response. Our studies suggest that what we eat plays a determinant role in our capacity to fine tune the inflammatory response. Introduction
Publisher: Springer Science and Business Media LLC
Date: 05-01-2016
DOI: 10.1007/S11060-015-2043-3
Abstract: Malignant gliomas are a lethal type of brain tumors that poorly respond to chemotherapeutic drugs. Several therapy resistance mechanisms have been characterized. However, the response to stress through mRNA translational control has not been evaluated for this type of tumor. A potential target would involve the alpha subunit of eukaryotic translation initiation factor (eIF2α) that leads to assembly of stress granules (SG) which are cytoplasmic granules mainly composed by RNA binding proteins and untranslated mRNAs. We assessed whether glioma cells are capable of assembling SG after exposure to different classes of chemotherapeutic agents through evaluation of the effects of interfering in this process by impairing the eIF2α signaling. C6 and U87MG cells were exposed to bortezomib, cisplatin, or etoposide. Forced expression of a dominant negative mutant of eIF2α (eIF2α(DN)) was employed to block this pathway. We observed that exposure to drugs stimulated SG assembly. This was reduced in eIF2α(DN)-transfected cells and this strategy enhanced chemotherapeutically-induced cell death for all drugs. Our data suggest that SG assembly occurs in glioma cells in response to chemotherapeutic drugs in an eIF2α-dependent manner and this response is relevant for drug resistance. Interfering with eIF2α signaling pathway may be a potential strategy for new co-adjuvant therapies to treat gliomas.
Publisher: MDPI AG
Date: 03-02-2022
Abstract: Pneumonia is a leading cause of morbidity and mortality. While inflammation is a host protective response that ensures bacterial clearance, a finely regulated response is necessary to prevent bystander tissue damage. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a GC-induced protein with anti-inflammatory and proresolving bioactions, yet the therapeutical role of GILZ in infectious diseases remains unexplored. Herein, we investigate the role and effects of GILZ during acute lung injury (ALI) induced by LPS and Streptococcus pneumoniae infection. GILZ deficient mice (GILZ−/−) presented more severe ALI, characterized by increased inflammation, decreased macrophage efferocytosis and pronounced lung damage. In contrast, pulmonary inflammation, and damage were attenuated in WT mice treated with TAT-GILZ fusion protein. During pneumococcal pneumonia, TAT-GILZ reduced neutrophilic inflammation and prevented the associated lung damage. There was also enhanced macrophage efferocytosis and bacterial clearance in TAT-GILZ-treated mice. Mechanistically, TAT-GILZ enhanced macrophage phagocytosis of pneumococcus, which was lower in GILZ−/− macrophages. Noteworthy, early treatment with TAT-GILZ rescued 30% of S. pneumoniae-infected mice from lethal pneumonia. Altogether, we present evidence that TAT-GILZ enhances host resilience and resistance to pneumococcal pneumonia by controlling pulmonary inflammation and bacterial loads leading to decreased lethality. Exploiting GILZ pathways holds promise for the treatment of severe respiratory infections.
No related grants have been discovered for Lirlândia Sousa.