Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation
Interleukin- (IL-) 17A, a pleiotropic mediator of inflammation and autoimmunity, potently stimulates bone-marrow neutrophil production. To explore IL-17A effects on eosinopoiesis, we cultured bone-marrow from wild-type mice, or mutants lacking inducible nitric oxide synthase (iNOS−/−), CD95 (lpr),...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/968932 |
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| author | Pedro Xavier-Elsas Bianca de Luca Túlio Queto Bruno Marques Vieira Daniela Masid-de-Brito Elizabeth Chen Dahab José Carlos Alves Filho Fernando Q. Cunha Maria Ignez C. Gaspar-Elsas |
| author_facet | Pedro Xavier-Elsas Bianca de Luca Túlio Queto Bruno Marques Vieira Daniela Masid-de-Brito Elizabeth Chen Dahab José Carlos Alves Filho Fernando Q. Cunha Maria Ignez C. Gaspar-Elsas |
| author_sort | Pedro Xavier-Elsas |
| collection | DOAJ |
| description | Interleukin- (IL-) 17A, a pleiotropic mediator of inflammation and autoimmunity, potently stimulates bone-marrow neutrophil production. To explore IL-17A effects on eosinopoiesis, we cultured bone-marrow from wild-type mice, or mutants lacking inducible nitric oxide synthase (iNOS−/−), CD95 (lpr), IL-17RA, or IL-4, with IL-5, alone or associated with IL-17A. Synergisms between IL-17A-activated, NO-dependent, and NO-independent mechanisms and antagonisms between IL-17A and proallergic factors were further examined. While IL-17A (0.1–10 ng/mL) had no IL-5-independent effect on eosinopoiesis, it dose-dependently suppressed IL-5-induced eosinophil differentiation, by acting during the initial 24 hours. Its effectiveness was abolished by caspase inhibitor, zVAD-fmk. The effect of IL-17A (0.1–1 ng/mL) was sensitive to the iNOS-selective inhibitor aminoguanidine and undetectable in iNOS−/− bone-marrow. By contrast, a higher IL-17A concentration (10 ng/mL) retained significant suppressive effect in both conditions, unmasking a high-end iNOS-independent mechanism. Lower IL-17A concentrations synergized with NO donor nitroprusside. Eosinopoiesis suppression by IL-17A was (a) undetectable in bone-marrow lacking IL-17RA or CD95 and (b) actively prevented by LTD4, LTC4, IL-13, and eotaxin. Sensitivity to IL-17A was increased in bone-marrow lacking IL-4; adding IL-4 to the cultures restored IL-5 responses to control levels. Therefore, effects of both IL-17A and proallergic factors are transduced by the iNOS-CD95 pathway in isolated bone-marrow. |
| format | Article |
| id | doaj-art-bcd742229b114de4b8cd21aa276fd858 |
| institution | DOAJ |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-bcd742229b114de4b8cd21aa276fd8582025-08-20T03:23:18ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/968932968932Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic InflammationPedro Xavier-Elsas0Bianca de Luca1Túlio Queto2Bruno Marques Vieira3Daniela Masid-de-Brito4Elizabeth Chen Dahab5José Carlos Alves Filho6Fernando Q. Cunha7Maria Ignez C. Gaspar-Elsas8Department of Immunology, Paulo de Góes Institute for Microbiology, Federal University of Rio de Janeiro (UFRJ), 21941-590 Rio de Janeiro, RJ, BrazilDepartment of Pediatrics, Fernandes Figueira National Institute for Health of Women, Children and Adolescents, Oswaldo Cruz Foundation (FIOCRUZ), 22250-020 Rio de Janeiro, RJ, BrazilDepartment of Pediatrics, Fernandes Figueira National Institute for Health of Women, Children and Adolescents, Oswaldo Cruz Foundation (FIOCRUZ), 22250-020 Rio de Janeiro, RJ, BrazilDepartment of Pediatrics, Fernandes Figueira National Institute for Health of Women, Children and Adolescents, Oswaldo Cruz Foundation (FIOCRUZ), 22250-020 Rio de Janeiro, RJ, BrazilDepartment of Immunology, Paulo de Góes Institute for Microbiology, Federal University of Rio de Janeiro (UFRJ), 21941-590 Rio de Janeiro, RJ, BrazilDepartment of Immunology, Paulo de Góes Institute for Microbiology, Federal University of Rio de Janeiro (UFRJ), 21941-590 Rio de Janeiro, RJ, BrazilDepartment of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, BrazilDepartment of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, BrazilDepartment of Pediatrics, Fernandes Figueira National Institute for Health of Women, Children and Adolescents, Oswaldo Cruz Foundation (FIOCRUZ), 22250-020 Rio de Janeiro, RJ, BrazilInterleukin- (IL-) 17A, a pleiotropic mediator of inflammation and autoimmunity, potently stimulates bone-marrow neutrophil production. To explore IL-17A effects on eosinopoiesis, we cultured bone-marrow from wild-type mice, or mutants lacking inducible nitric oxide synthase (iNOS−/−), CD95 (lpr), IL-17RA, or IL-4, with IL-5, alone or associated with IL-17A. Synergisms between IL-17A-activated, NO-dependent, and NO-independent mechanisms and antagonisms between IL-17A and proallergic factors were further examined. While IL-17A (0.1–10 ng/mL) had no IL-5-independent effect on eosinopoiesis, it dose-dependently suppressed IL-5-induced eosinophil differentiation, by acting during the initial 24 hours. Its effectiveness was abolished by caspase inhibitor, zVAD-fmk. The effect of IL-17A (0.1–1 ng/mL) was sensitive to the iNOS-selective inhibitor aminoguanidine and undetectable in iNOS−/− bone-marrow. By contrast, a higher IL-17A concentration (10 ng/mL) retained significant suppressive effect in both conditions, unmasking a high-end iNOS-independent mechanism. Lower IL-17A concentrations synergized with NO donor nitroprusside. Eosinopoiesis suppression by IL-17A was (a) undetectable in bone-marrow lacking IL-17RA or CD95 and (b) actively prevented by LTD4, LTC4, IL-13, and eotaxin. Sensitivity to IL-17A was increased in bone-marrow lacking IL-4; adding IL-4 to the cultures restored IL-5 responses to control levels. Therefore, effects of both IL-17A and proallergic factors are transduced by the iNOS-CD95 pathway in isolated bone-marrow.http://dx.doi.org/10.1155/2015/968932 |
| spellingShingle | Pedro Xavier-Elsas Bianca de Luca Túlio Queto Bruno Marques Vieira Daniela Masid-de-Brito Elizabeth Chen Dahab José Carlos Alves Filho Fernando Q. Cunha Maria Ignez C. Gaspar-Elsas Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation Mediators of Inflammation |
| title | Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation |
| title_full | Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation |
| title_fullStr | Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation |
| title_full_unstemmed | Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation |
| title_short | Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation |
| title_sort | blockage of eosinopoiesis by il 17a is prevented by cytokine and lipid mediators of allergic inflammation |
| url | http://dx.doi.org/10.1155/2015/968932 |
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