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Mediators of Inflammation
Volume 2015 (2015), Article ID 968932, 11 pages
Research Article

Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation

1Department of Immunology, Paulo de Góes Institute for Microbiology, Federal University of Rio de Janeiro (UFRJ), 21941-590 Rio de Janeiro, RJ, Brazil
2Department of Pediatrics, Fernandes Figueira National Institute for Health of Women, Children and Adolescents, Oswaldo Cruz Foundation (FIOCRUZ), 22250-020 Rio de Janeiro, RJ, Brazil
3Department of Pharmacology, Medical School of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil

Received 23 December 2014; Revised 15 April 2015; Accepted 15 April 2015

Academic Editor: Hannes Neuwirt

Copyright © 2015 Pedro Xavier-Elsas et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.