Omega-9 Oleic Acid, the Main Compound of Olive Oil, Mitigates Inflammation during Experimental Sepsis

The Mediterranean diet, rich in olive oil, is beneficial, reducing the risk of cardiovascular diseases and cancer. Olive oil is mostly composed of the monounsaturated fatty acid omega-9. We showed omega-9 protects septic mice modulating lipid metabolism. Sepsis is initiated by the host response to infection with organ damage, increased plasma free fatty acids, high levels of cortisol, massive cytokine production, leukocyte activation, and endothelial dysfunction. We aimed to analyze the effect of omega-9 supplementation on corticosteroid unbalance, inflammation, bacterial elimination, and peroxisome proliferator-activated receptor (PPAR) gamma expression, an omega-9 receptor and inflammatory modulator. We treated mice for 14 days with omega-9 and induced sepsis by cecal ligation and puncture (CLP). We measured systemic corticosterone levels, cytokine production, leukocyte and bacterial counts in the peritoneum, and the expression of PPAR gamma in both liver and adipose tissues during experimental sepsis. We further studied omega-9 effects on leukocyte rolling in mouse cremaster muscle-inflamed postcapillary venules and in the cerebral microcirculation of septic mice. Here, we demonstrate that omega-9 treatment is associated with increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the proinflammatory cytokines TNF-alpha and IL-1 beta in peritoneal lavage fluid of mice with sepsis. Omega-9 treatment also decreased systemic corticosterone levels. Neutrophil migration from circulation to the peritoneal cavity and leukocyte rolling on the endothelium were decreased by omega-9 treatment. Omega-9 also decreased bacterial load in the peritoneal lavage and restored liver and adipose tissue PPAR gamma expression in septic animals. Our data suggest a beneficial anti-inflammatory role of omega-9 in sepsis, mitigating leukocyte rolling and leukocyte influx, balancing cytokine production, and controlling bacterial growth possibly through a PPAR gamma expression-dependent mechanism. The significant reduction of inflammation detected after omega-9 enteral injection can further contribute to the already known beneficial properties facilitated by unsaturated fatty acid-enriched diets

Immunization of Experimental Dogs With Salivary Proteins From Lutzomyia longipalpis, Using DNA and Recombinant Canarypox Virus Induces Immune Responses Consistent With Protection Against Leishmania infantum

Metacyclic Leishmania promastigotes are transmitted by sand flies that inject parasites and saliva into the host's skin. Previous studies have demonstrated that DNA plasmids encoding Lutzomyia longipalpis salivary proteins LJM17 and LJL143, when used to immunize dogs, resulted in a systemic and local Th1 cell-mediated immunity that interfered in parasite survival in vitro. Here we evaluated the ability of these same salivary antigens to induce anti-Leishmania immunity and to confer protection by immunizing dogs using a novel vaccination strategy more suitable for use in the field. The strategy consisted of a single dose of plasmid followed by two doses of recombinant Canarypoxvirus (rCanarypoxvirus) expressing L. longipalpis salivary proteins (LJM17 or LJL143). Thirty days after the final immunization, dogs were intradermally challenged with 107Leishmania infantum promastigotes in the presence of L. longipalpis saliva. We followed the experimentally infected dogs for 10 months to characterize clinical, parasitological, and immunological parameters. Upon vaccination, all immunized dogs presented strong and specific humoral responses with increased serum concentrations of IFN-γ, TNF, IL-7, and IL-15. The serum of dogs immunized with LJM17 also exhibited high levels of IL-2, IL-6, and IL-18. L. infantum infection was established in all experimental groups as evidenced by the presence of anti-Leishmania IgG, and by parasite detection in the spleen and skin. Dogs immunized with LJM17-based vaccines presented higher circulating levels of IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-18, TNF, CXCL10, and GM-CSF post-infection when compared with controls. Results demonstrated that relevant Leishmania-specific immune responses were induced following vaccination of dogs with L. longipalpis salivary antigen LJM17 administered in a single priming dose of plasmid DNA, followed by two booster doses of recombinant Canarypox vector. Importantly, a significant increase in pro-inflammatory cytokines and chemokines known to be relevant for protection against leishmaniasis was evidenced after challenging LJM17-vaccinated dogs as compared to controls. Although similar results were observed following immunization with LJL143, the pro-inflammatory response observed after immunization was attenuated following infection. Collectively, these data suggest that the LJM17-based vaccine induced an immune profile consistent with the expected protective immunity against canine leishmaniosis. These results clearly support the need for further evaluation of the LJM17 antigen, using a heterologous prime-boost vaccination strategy against canine visceral leishmaniosis (CVL)

Hepatic myofibroblasts derived from Schistosoma mansoni-infected mice are a source of IL-5 and eotaxin: controls of eosinophil populations in vitro

Abstract Background Hepatic myofibroblasts are relevant for pathogenesis of S. mansoni infection. In normal liver, these perisinusoidal cells are quiescent, express the lipocyte phenotype, and are located in the Disse’s space, being the major site of vitamin A storage. When activated, they convert to myofibroblasts and contribute to granulomatous and diffuse liver fibrosis. In the present work, we observed that myofibroblasts obtained from granulomatous periovular inflammatory reactions in schistosome-infected mice (GR-MF) produce in vitro immunomodulatory cytokines for eosinophil activation: IL-5 and eotaxin. Methods and results The secretory activity of GR-MF was detected after TGF-β and IL-13 stimulation using 2D and 3D cell culture systems. In a mixed co-culture system using GR-MF with hematopoietic bone marrow cells from infected mice, we observed eosinophil survival that was dependent upon IL-5 and eotaxin, since antibodies against this cytokines decreased eosinophil population, as measured by eosinophil peroxidase activity. Conclusion These results indicate that GR-MF may contribute to maintenance of local eosinophilia in schistosomal hepatic granulomas, and can function as immunoregulatory cells, besides their role in production of fibrosis

Integrin αDβ2 (CD11d/CD18) Modulates Leukocyte Accumulation, Pathogen Clearance, and Pyroptosis in Experimental Salmonella Typhimurium Infection

Submitted by Sandra Infurna ([email protected]) on 2018-10-05T18:50:13Z No. of bitstreams: 1 angelica_arcanjo_etal_IOC_2018.pdf: 2797972 bytes, checksum: 37f8e14929f42c3fe6355259397ae0a4 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-10-05T18:59:42Z (GMT) No. of bitstreams: 1 angelica_arcanjo_etal_IOC_2018.pdf: 2797972 bytes, checksum: 37f8e14929f42c3fe6355259397ae0a4 (MD5)Made available in DSpace on 2018-10-05T18:59:42Z (GMT). No. of bitstreams: 1 angelica_arcanjo_etal_IOC_2018.pdf: 2797972 bytes, checksum: 37f8e14929f42c3fe6355259397ae0a4 (MD5) Previous issue date: 2018Fundação 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 / University of Utah School of Medicine. Department of Internal Medicine. Salt Lake City, UT, USA.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.University of Utah School of Medicine. Department of Internal Medicine. Salt Lake City, UT, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.β2 integrins are critical in host defense responses to invading pathogens and inflammation. Previously, we reported that genetic deficiency of integrin αDβ2 in mice altered outcomes in experimental systemic infections including accelerated mortality in animals infected with Salmonella enterica serovar Typhimurium. Here, we show that deficiency of αDβ2 results in impaired accumulation of leukocytes in response to peritoneal infection by S. Typhimurium, impaired pathogen clearance in vivo, defective bacterial elimination by cultured peritoneal macrophages, and enhanced pyroptosis, a cell death process triggered by Salmonella. Salmonella-infected animals deficient in αDβ2 had increased levels of peritoneal cytokines in addition to other markers of pyroptosis, which may contribute to inflammatory injury and increased mortality in the context of impaired bacterial killing. These observations indicate important contributions of leukocyte integrins to the host response in experimental Salmonella infection and reveal previous activities of αDβ2 in bacterial infection

Enterolobin induces rat paw oedema independently of PAF-Acether

The potential participation of PAF-acether (PAF) on the paw oedema triggered by enterolobin was investigated. Intraplantar injections of enterolobin (5-20 µg/paw) yielded a dose response curve for oedema which appeared after 30 min, peaked in the interval between 2-4 h and faded after 24 h. The pre-treatment with BN 52021, but not with other PAF antagonists such as PCA 4248 or WEB 2086, significantly blocked enterolobin-induced oedema. To clarify better the discrepant results obtained with the PAF antagonists, desensitization to PAF was perfomed. The oedema triggered by enterolobin was not modified in PAF desensitized animals. It was concluded that the paw inflammation induced by enterolobin does not require PAF mechanism

image_5_Integrin αDβ2 (CD11d/CD18) Modulates Leukocyte Accumulation, Pathogen Clearance, and Pyroptosis in Experimental Salmonella Typhimurium Infection.pdf

<p>β₂ integrins are critical in host defense responses to invading pathogens and inflammation. Previously, we reported that genetic deficiency of integrin α_Dβ₂ in mice altered outcomes in experimental systemic infections including accelerated mortality in animals infected with Salmonella enterica serovar Typhimurium. Here, we show that deficiency of α_Dβ₂ results in impaired accumulation of leukocytes in response to peritoneal infection by S. Typhimurium, impaired pathogen clearance in vivo, defective bacterial elimination by cultured peritoneal macrophages, and enhanced pyroptosis, a cell death process triggered by Salmonella. Salmonella-infected animals deficient in α_Dβ₂ had increased levels of peritoneal cytokines in addition to other markers of pyroptosis, which may contribute to inflammatory injury and increased mortality in the context of impaired bacterial killing. These observations indicate important contributions of leukocyte integrins to the host response in experimental Salmonella infection and reveal previous activities of α_Dβ₂ in bacterial infection.</p

image_1_Integrin αDβ2 (CD11d/CD18) Modulates Leukocyte Accumulation, Pathogen Clearance, and Pyroptosis in Experimental Salmonella Typhimurium Infection.pdf

<p>β₂ integrins are critical in host defense responses to invading pathogens and inflammation. Previously, we reported that genetic deficiency of integrin α_Dβ₂ in mice altered outcomes in experimental systemic infections including accelerated mortality in animals infected with Salmonella enterica serovar Typhimurium. Here, we show that deficiency of α_Dβ₂ results in impaired accumulation of leukocytes in response to peritoneal infection by S. Typhimurium, impaired pathogen clearance in vivo, defective bacterial elimination by cultured peritoneal macrophages, and enhanced pyroptosis, a cell death process triggered by Salmonella. Salmonella-infected animals deficient in α_Dβ₂ had increased levels of peritoneal cytokines in addition to other markers of pyroptosis, which may contribute to inflammatory injury and increased mortality in the context of impaired bacterial killing. These observations indicate important contributions of leukocyte integrins to the host response in experimental Salmonella infection and reveal previous activities of α_Dβ₂ in bacterial infection.</p

image_2_Integrin αDβ2 (CD11d/CD18) Modulates Leukocyte Accumulation, Pathogen Clearance, and Pyroptosis in Experimental Salmonella Typhimurium Infection.pdf

<p>β₂ integrins are critical in host defense responses to invading pathogens and inflammation. Previously, we reported that genetic deficiency of integrin α_Dβ₂ in mice altered outcomes in experimental systemic infections including accelerated mortality in animals infected with Salmonella enterica serovar Typhimurium. Here, we show that deficiency of α_Dβ₂ results in impaired accumulation of leukocytes in response to peritoneal infection by S. Typhimurium, impaired pathogen clearance in vivo, defective bacterial elimination by cultured peritoneal macrophages, and enhanced pyroptosis, a cell death process triggered by Salmonella. Salmonella-infected animals deficient in α_Dβ₂ had increased levels of peritoneal cytokines in addition to other markers of pyroptosis, which may contribute to inflammatory injury and increased mortality in the context of impaired bacterial killing. These observations indicate important contributions of leukocyte integrins to the host response in experimental Salmonella infection and reveal previous activities of α_Dβ₂ in bacterial infection.</p

Yangambin, a lignan obtained from Ocotea duckei, differentiates putative PAF receptor subtypes in the gastrointestinal tract of rats

Submitted by Alexandre Sousa ([email protected]) on 2015-11-10T17:09:29Z No. of bitstreams: 1 Planta_Medica_66_211-216.pdf: 179561 bytes, checksum: 88dca5c5600e41c82146c75bd00eae05 (MD5)Approved for entry into archive by Alexandre Sousa ([email protected]) on 2015-11-10T17:37:29Z (GMT) No. of bitstreams: 1 Planta_Medica_66_211-216.pdf: 179561 bytes, checksum: 88dca5c5600e41c82146c75bd00eae05 (MD5)Made available in DSpace on 2015-11-10T17:37:29Z (GMT). No. of bitstreams: 1 Planta_Medica_66_211-216.pdf: 179561 bytes, checksum: 88dca5c5600e41c82146c75bd00eae05 (MD5) Previous issue date: 2000Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Química. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade de São Paulo. Instituto de Ciências Biomédicas. São Paulo, SP, Brasil.Universidade de São Paulo. Instituto de Ciências Biomédicas. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Fisiologia e Farmacodinâmica. Rio de Janeiro, RJ, Brasil.We investigated the presence of PAF receptor subtypes in the tissues of the gastrointestinal tract, airways, blood vessels and in murine macrophages. For this purpose we have used a competitive PAF receptor antagonist, yangambin (YAN), extracted from the Brazilian plant “louro de cheiro” (Ocotea duckei Vattimo). Rat duodenum, jejunum, ileum, colon, stomach fundus, trachea and bronchia were removed and 1.5 - 2 cm muscle segments from those regions were mounted in a 10 ml organ bath with aerated physiological solution at 37 °C. PAF evoked a contraction of the rat jejunum, ileum, colon and stomach fundus. The contraction was slow and resistant to wash and was followed by desensitization to further doses of PAF. Contractions induced by PAF (10-6 M) were inhibited by YAN (10-7 to M - 2 × 10-5 M) and WEB 2086 (10-6 m to M-5 M) in rat jejunum, ileum and colon but not in the stomach fundus. In the rat stomach fundus only WEB 2086 (5 × 10-6 M) was able to block PAF-induced contraction. The contractions induced by acetylcholine, histamine, 5-hydroxytryptamine and vasopressin were not inhibited by prior administration of YAN. Yangambin also significantly inhibited PAF-induced vascular permeability in rat duodenum, jejunum, ileum, colon, and mesentery. Yangambin significantly inhibited PAF-induced lipid body formation in mice peritoneal macrophages. We suggest that YAN is a selective PAF antagonist which is able to discriminate putative PAF receptors subtypes present in the stomach fundus