Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents
Up- and downregulation of eosinopoiesis control pulmonary eosinophilia in human asthma. In mice, eosinopoiesis is suppressed in vitro by prostaglandin E2 (PGE2) and in vivo by diethylcarbamazine, through a proapoptotic mechanism sequentially requiring inducible NO synthase (iNOS) and the ligand for...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2013/208705 |
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| author | Bianca de Luca Pedro Xavier-Elsas Mônica Barradas Ricardo A. Luz Túlio Queto Carla Jones Maria Augusta Arruda Thiago Mattar Cunha Fernando Queiroz Cunha Maria Ignez Gaspar-Elsas |
| author_facet | Bianca de Luca Pedro Xavier-Elsas Mônica Barradas Ricardo A. Luz Túlio Queto Carla Jones Maria Augusta Arruda Thiago Mattar Cunha Fernando Queiroz Cunha Maria Ignez Gaspar-Elsas |
| author_sort | Bianca de Luca |
| collection | DOAJ |
| description | Up- and downregulation of eosinopoiesis control pulmonary eosinophilia in human asthma. In mice, eosinopoiesis is suppressed in vitro by prostaglandin E2 (PGE2) and in vivo by diethylcarbamazine, through a proapoptotic mechanism sequentially requiring inducible NO synthase (iNOS) and the ligand for death receptor CD95 (CD95L). We examined the roles of iNOS, cAMP-mediated signaling, caspases, and CD95L/CD95 in suppression of eosinopoiesis by PGE2 and other agents signaling through cAMP. Bone-marrow collected from BALB/c mice, or from iNOS-, CD95-, or CD95L-deficient mutants (and wild-type controls), was cultured with interleukin-5 (IL-5), alone or associated with PGE2, cAMP-inducing/mimetic agents, caspase inhibitor zVAD-fmk, iNOS inhibitor aminoguanidine, or combinations thereof, and eosinopoiesis was evaluated at various times. PGE2, added up to 24 hours of culture, dose-dependently suppressed eosinopoiesis, by inducing apoptosis. This effect was (a) paralleled by induction of iNOS in eosinophils; (b) duplicated by sodium nitroprusside, isoproterenol, and cAMP-inducing/mimetic agents; (c) prevented by protein kinase A inhibition. NO was produced through iNOS by dibutyryl-cAMP-stimulated bone-marrow. Overall, PGE2 and isoproterenol shared a requirement for four effector elements (iNOS, CD95L, CD95, and terminal caspases), which together define a pathway targeted by several soluble up- and downmodulators of eosinopoiesis, including drugs, mediators of inflammation, and cytokines. |
| format | Article |
| id | doaj-art-84ce1afd2f394b33a3fb8851537d3abd |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-84ce1afd2f394b33a3fb8851537d3abd2025-02-03T01:12:01ZengWileyThe Scientific World Journal1537-744X2013-01-01201310.1155/2013/208705208705Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating AgentsBianca de Luca0Pedro Xavier-Elsas1Mônica Barradas2Ricardo A. Luz3Túlio Queto4Carla Jones5Maria Augusta Arruda6Thiago Mattar Cunha7Fernando Queiroz Cunha8Maria Ignez Gaspar-Elsas9Department of Pediatrics, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, Avenue Rui Barbosa 716, 22250-020 Rio de Janeiro, RJ, BrazilDepartment of Immunology, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 22205-020, Rio de Janeiro, BrazilDepartment of Immunology, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 22205-020, Rio de Janeiro, BrazilDepartment of Immunology, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 22205-020, Rio de Janeiro, BrazilDepartment of Pediatrics, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, Avenue Rui Barbosa 716, 22250-020 Rio de Janeiro, RJ, BrazilDepartment of Immunology, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, CCS, Bloco I, Room I-2-066, 22205-020, Rio de Janeiro, BrazilFarmanguinhos, FIOCRUZ, Avenue Comandante Guaranys No. 447, Jacarepaguá, 22775-903 Rio de Janeiro, RJ, BrazilDepartment of Pharmacology, Faculdade de Medicina da USP, Avenue Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, BrazilDepartment of Pharmacology, Faculdade de Medicina da USP, Avenue Bandeirantes 3900, Monte Alegre, 14049-900 Ribeirão Preto, SP, BrazilDepartment of Pediatrics, Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira, FIOCRUZ, Avenue Rui Barbosa 716, 22250-020 Rio de Janeiro, RJ, BrazilUp- and downregulation of eosinopoiesis control pulmonary eosinophilia in human asthma. In mice, eosinopoiesis is suppressed in vitro by prostaglandin E2 (PGE2) and in vivo by diethylcarbamazine, through a proapoptotic mechanism sequentially requiring inducible NO synthase (iNOS) and the ligand for death receptor CD95 (CD95L). We examined the roles of iNOS, cAMP-mediated signaling, caspases, and CD95L/CD95 in suppression of eosinopoiesis by PGE2 and other agents signaling through cAMP. Bone-marrow collected from BALB/c mice, or from iNOS-, CD95-, or CD95L-deficient mutants (and wild-type controls), was cultured with interleukin-5 (IL-5), alone or associated with PGE2, cAMP-inducing/mimetic agents, caspase inhibitor zVAD-fmk, iNOS inhibitor aminoguanidine, or combinations thereof, and eosinopoiesis was evaluated at various times. PGE2, added up to 24 hours of culture, dose-dependently suppressed eosinopoiesis, by inducing apoptosis. This effect was (a) paralleled by induction of iNOS in eosinophils; (b) duplicated by sodium nitroprusside, isoproterenol, and cAMP-inducing/mimetic agents; (c) prevented by protein kinase A inhibition. NO was produced through iNOS by dibutyryl-cAMP-stimulated bone-marrow. Overall, PGE2 and isoproterenol shared a requirement for four effector elements (iNOS, CD95L, CD95, and terminal caspases), which together define a pathway targeted by several soluble up- and downmodulators of eosinopoiesis, including drugs, mediators of inflammation, and cytokines.http://dx.doi.org/10.1155/2013/208705 |
| spellingShingle | Bianca de Luca Pedro Xavier-Elsas Mônica Barradas Ricardo A. Luz Túlio Queto Carla Jones Maria Augusta Arruda Thiago Mattar Cunha Fernando Queiroz Cunha Maria Ignez Gaspar-Elsas Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents The Scientific World Journal |
| title | Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents |
| title_full | Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents |
| title_fullStr | Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents |
| title_full_unstemmed | Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents |
| title_short | Essential Roles of PKA, iNOS, CD95/CD95L, and Terminal Caspases in Suppression of Eosinopoiesis by PGE2 and Other cAMP-Elevating Agents |
| title_sort | essential roles of pka inos cd95 cd95l and terminal caspases in suppression of eosinopoiesis by pge2 and other camp elevating agents |
| url | http://dx.doi.org/10.1155/2013/208705 |
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