Lutzomyia longipalpis Saliva Triggers Lipid Body Formation and Prostaglandin E2 Production in Murine Macrophages

After the injection of saliva into the host's skin by sand flies, a transient erythematous reaction is observed, which is related to an influx of inflammatory cells and the release of various molecules that actively facilitate the blood meal. It is important to understand the specific mechanisms by which sand fly saliva manipulates the host's inflammatory responses. Herein, we report that saliva from Lutzomyia (L.) longipalpis, a widespread Leishmania vector, induces early production of eicosanoids. Intense formation of intracellular organelles called lipid bodies (LBs) was noted within those cells that migrated to the site of saliva injection. In vitro and ex vivo, sand fly saliva was able to induce LB formation and PGE2 release by macrophages. Interestingly, PGE2 production induced by L. longipalpis saliva was dependent on intracellular mechanisms involving phosphorylation of signaling proteins such as PKC-α and ERK-1/2 and subsequent activation of cyclooxygenase-2. Thus, this study provides new insights into the pharmacological properties of sand fly saliva and opens new opportunities for intervening with the induction of the host's inflammatory pathways by L. longipalpis bites

Sobre as políticas de produção e disseminação de conhecimento: diálogos com as políticas linguísticas

Neste artigo buscamos refletir sobre a dimensão política das práticas de produção e de disseminação de conhecimento, com enfoque na esfera acadêmica. A partir do âmbito das políticas linguísticas, debatemos o regime de produção de saberes legitimados, atentando para o papel da língua, especialmente aqueles localizados no Sul Global. O texto enfoca três elementos: (i) Em atenção aos movimentos #Rhodesmustfall e #Feesmustfall (2015-2017), buscamos refletir sobre o modelo de formação no ensino superior na África do Sul, incluindo políticas linguísticas a favor do multilinguismo e da a construção de horizontes que revertam a injustiça epistêmica. (ii) Além disso, em diálogo com o o Plano de Ação de Brasília (PAB) para a promoção, a difusão e a projeção da Língua Portuguesa, enfocamos a internacionalização da língua portuguesa, sinalizando para o papel desempenhado por essa língua em políticas tanto de inclusão, como de exclusão e invisibilização da diversidade cultural e linguística, especialmente na relação Sul-Sul; (iii) Em reconhecimento à importância da autoria na esfera de produção intelectual, discorremos sobre o conceito de lugar de fala e a política de citação com fins de problematizar a centralidade conferida aos pesquisadores, saberes e línguas do Norte, notadamente o inglês, na política de produção e disseminação. Finalmente, argumentamos que uma política que opere a favor da justiça epistêmica deve ser capaz de rever as regras do jogo, atentando para as relações históricas de poder que contribuiram para gerar geopolíticas e economias do conhecimento centrais e periféricas

PPARγ Expression and Function in Mycobacterial Infection: Roles in Lipid Metabolism, Immunity, and Bacterial Killing

Tuberculosis continues to be a global health threat, with drug resistance and HIV coinfection presenting challenges for its control. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is a highly adapted pathogen that has evolved different strategies to subvert the immune and metabolic responses of host cells. Although the significance of peroxisome proliferator-activated receptor gamma (PPARγ) activation by mycobacteria is not fully understood, recent findings are beginning to uncover a critical role for PPARγ during mycobacterial infection. Here, we will review the molecular mechanisms that regulate PPARγ expression and function during mycobacterial infection. Current evidence indicates that mycobacterial infection causes a time-dependent increase in PPARγ expression through mechanisms that involve pattern recognition receptor activation. Mycobacterial triggered increased PPARγ expression and activation lead to increased lipid droplet formation and downmodulation of macrophage response, suggesting that PPARγ expression might aid the mycobacteria in circumventing the host response acting as an escape mechanism. Indeed, inhibition of PPARγ enhances mycobacterial killing capacity of macrophages, suggesting a role of PPARγ in favoring the establishment of chronic infection. Collectively, PPARγ is emerging as a regulator of tuberculosis pathogenesis and an attractive target for the development of adjunctive tuberculosis therapies

Curine Inhibits Macrophage Activation and Neutrophil Recruitment in a Mouse Model of Lipopolysaccharide-Induced Inflammation

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2020-01-21T12:11:49Z No. of bitstreams: 1 Ribeiro-Filho j Curine Inhibits Tosins.pdf: 4153596 bytes, checksum: cc6b46647db9fe4e1ee57c25f4dcf6a8 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2020-01-21T12:21:53Z (GMT) No. of bitstreams: 1 Ribeiro-Filho j Curine Inhibits Tosins.pdf: 4153596 bytes, checksum: cc6b46647db9fe4e1ee57c25f4dcf6a8 (MD5)Made available in DSpace on 2020-01-21T12:21:53Z (GMT). No. of bitstreams: 1 Ribeiro-Filho j Curine Inhibits Tosins.pdf: 4153596 bytes, checksum: cc6b46647db9fe4e1ee57c25f4dcf6a8 (MD5) Previous issue date: 2019-01-03PRONEX/MCT, CNPq, FAPERJ and INCT-Câncer.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Investigação em Genética e Hematologia Translacional. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Laboratório de Pesquisa em Anemias. Departamento de Análises Clínicas e Toxicologicas. Salvador, BA, Brasil.Universidade Federal da Paraíba. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Patologia. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Laboratório de Fitoquímica. Departamento de Ciências Farmacêuticas. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Laboratório de Imunofarmacologia. Departamento de Fisiologia e Patologia. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Curine is a bisbenzylisoquinoline alkaloid (BBA) with anti-allergic, analgesic, and anti-inflammatory properties. Previous studies have demonstrated that this alkaloid is orally active at non-toxic doses. However, the mechanisms underlying its anti-inflammatory effects remain to be elucidated. This work aimed to investigate the effects of curine on macrophage activation and neutrophil recruitment. Using a murine model of lipopolysaccharide (LPS)-induced pleurisy, we demonstrated that curine significantly inhibited the recruitment of neutrophils in association with the inhibition of cytokines tumor necrosis factor (TNF-α), interleukin (IL)-1β, IL-6, monocyte chemotactic protein (CCL2/MCP-1) as well as leukotriene B4 in the pleural lavage of mice. Curine treatment reduced cytokine levels and the expression of iNOS in in vitro cultures of macrophages stimulated with LPS. Treatment with a calcium channel blocker resulted in comparable inhibition of TNF-α and IL-1β production, as well as iNOS expression by macrophages, suggesting that the anti-inflammatory effects of curine may be related to the inhibition of calcium-dependent mechanisms involved in macrophage activation. In conclusion, curine presented anti-inflammatory effects that are associated with inhibition of macrophage activation and neutrophil recruitment by inhibiting the production of inflammatory cytokines, LTB4 and nitric oxide (NO), and possibly by negatively modulating Ca2+ influx

Curine, an Alkaloid Isolated from Chondrodendron platyphyllum Inhibits Prostaglandin E2 in Experimental Models of Inflammation and Pain

Made available in DSpace on 2015-05-27T13:39:52Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) andrea_calheirosetal_IOC_2014.pdf: 179135 bytes, checksum: 2fd469793ee7706daa823c19306c4119 (MD5) Previous issue date: 2014Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Imunofarmacologia. João Pessoa, PB, Brasil .Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Imunofarmacologia. João Pessoa, PB, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Imunofarmacologia. João Pessoa, PB, Brasil .Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Psicofarmacologia. João Pessoa, PB, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Departamento de Fisiologia e Patologia. Laboratório de Psicofarmacologia. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Departamento de Ciências Farmacêuticas. Laboratório de Fitoquímica. João Pessoa, PB, Brasil.Curine is a bisbenzylisoquinoline alkaloid that is isolated from Chondrodendron platyphyllum, a plant that is used to treat malaria, inflammation, and pain. Recent reports have demonstrated the antiallergic effects of curine at nontoxic doses. However, its anti-inflammatory and analgesic properties remain to be elucidated. This study investigated the anti-inflammatory and analgesic effects of curine in mice. We analyzed the effects of an oral treatment with curine in the formation of paw edema, vascular permeability, abdominal contortion, licking behavior, and hyperalgesia using different inflammatory stimuli. Curine significantly inhibited the formation of paw edema by decreasing vascular permeability, inhibited the acetic acid-induced writhing response, inhibited the licking behavior during inflammation but not during the neurogenic phase of the formalin test, and inhibited carrageenan-induced hyperalgesia. Finally, curine inhibited prostaglandin E2 production in vitro without affecting cyclooxygenase-2 expression. The effects of curine treatment were similar to the effects of indomethacin, but were different from the effects of morphine treatment, suggesting that the analgesic effects of curine do not result from the direct inhibition of neuronal activation but instead depend on anti-inflammatory mechanisms that, at least in part, result from the inhibition of prostaglandin E2 production. In conclusion, curine presents anti-inflammatory and analgesic effects at nontoxic doses and has the potential for use in anti-inflammatory drug development

Lysophosphatidylcholine Triggers TLR2- and TLR4- Mediated Signaling Pathways but Counteracts LPSInduced NO Synthesis in Peritoneal Macrophages by Inhibiting NF-κB Translocation and MAPK/ERK Phosphorylation

Made available in DSpace on 2015-09-28T13:02:39Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) igor_almeida_etal_IOC_2013.pdf: 680569 bytes, checksum: 68dcc939113bc5eb10c5deee819a7ff8 (MD5) Previous issue date: 2013Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil.University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular Patogênicos. Ribeirão Preto, SP, Brasil.University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA.University of Texas at El Paso. Department of Biological Sciences. The Border Biomedical Research Center. El Paso, Texas, USA / Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Biologia Celular e Molecular Patogênicos. Ribeirão Preto, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Parasitologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica. Programa de Biologia Molecular e Biotecnologia. Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular- INCT-EM. Rio de Janeiro, RJ, Brasil.Background: Lysophosphatidylcholine (LPC) is the main phospholipid component of oxidized low-density lipoprotein (oxLDL) and is usually noted as a marker of several human diseases, such as atherosclerosis, cancer and diabetes. Some studies suggest that oxLDL modulates Toll-like receptor (TLR) signaling. However, effector molecules that are present in oxLDL particles and can trigger TLR signaling are not yet clear. LPC was previously described as an attenuator of sepsis and as an immune suppressor. In the present study, we have evaluated the role of LPC as a dual modulator of the TLR-mediated signaling pathway. Methodology/Principal Findings: HEK 293A cells were transfected with TLR expression constructs and stimulated with LPC molecules with different fatty acid chain lengths and saturation levels. All LPC molecules activated both TLR4 and TLR2-1 signaling, as evaluated by NF-қB activation and IL-8 production. These data were confirmed by Western blot analysis of NF-қB translocation in isolated nuclei of peritoneal murine macrophages. However, LPC counteracted the TLR4 signaling induced by LPS. In this case, NF-қB translocation, nitric oxide (NO) synthesis and the expression of inducible nitric oxide synthase (iNOS) were blocked. Moreover, LPC activated the MAP Kinases p38 and JNK, but not ERK, in murine macrophages. Interestingly, LPC blocked LPS-induced ERK activation in peritoneal macrophages but not in TLR-transfected cells. Conclusions/Significance: The above results indicate that LPC is a dual-activity ligand molecule. It is able to trigger a classical proinflammatory phenotype by activating TLR4- and TLR2-1-mediated signaling. However, in the presence of classical TLR ligands, LPC counteracts some of the TLR-mediated intracellular responses, ultimately inducing an anti-inflammatory phenotype; LPC may thus play a role in the regulation of cell immune responses and disease progression

Leishmania infantum lipophosphoglycan induced-Prostaglandin E2production in association with PPAR-γ expression via activation of Toll like receptors-1 and 2

Submitted by Sandra Infurna ([email protected]) on 2018-02-20T14:30:30Z No. of bitstreams: 1 alan_carneiro_etal_IOC_2017.pdf: 1888939 bytes, checksum: b9e4323376f30ec53fccc102bfc178bc (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-02-20T14:45:35Z (GMT) No. of bitstreams: 1 alan_carneiro_etal_IOC_2017.pdf: 1888939 bytes, checksum: b9e4323376f30ec53fccc102bfc178bc (MD5)Made available in DSpace on 2018-02-20T14:45:35Z (GMT). No. of bitstreams: 1 alan_carneiro_etal_IOC_2017.pdf: 1888939 bytes, checksum: b9e4323376f30ec53fccc102bfc178bc (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal do Oeste da Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal do Oeste da Bahia. Centro de Ciências Biológicas e da Saúde. Barreiras, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Universidade Federal do Rio de Janeiro. NUPEM. Campus Macaé. macaé, RJ, Brasil.Institut National de la Recherche Scientifique. Institut Armand-Frappier. Laval, Canada.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Salvador, BA, Brasil.Lipophosphoglycan (LPG) is a key virulence factor expressed on the surfaces of Leishmania promastigotes. Although LPG is known to activate macrophages, the underlying mechanisms resulting in the production of prostaglandin E2(PGE2) via signaling pathways remain unknown. Here, the inflammatory response arising from stimulation by Leishmania infantum LPG and/or its lipid and glycan motifs was evaluated with regard to PGE2induction. Intact LPG, but not its glycan and lipid moieties, induced a range of proinflammatory responses, including PGE2and nitric oxide (NO) release, increased lipid droplet formation, and iNOS and COX2 expression. LPG also induced ERK-1/2 and JNK phosphorylation in macrophages, in addition to the release of PGE2, MCP-1, IL-6, TNF-α and IL-12p70, but not IL-10. Pharmacological inhibition of ERK1/2 and PKC affected PGE2and cytokine production. Moreover, treatment with rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ), also modulated the release of PGE2and other proinflammatory mediators. Finally, we determined that LPG-induced PPAR-γ signaling occurred via TLR1/2. Taken together, these results reinforce the role played by L. infantum-derived LPG in the proinflammatory response seen in Leishmania infection