Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection

Prostaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum inf...

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Main Authors: Priscilla Aparecida Tartari Pereira, Bruno Caetano Trindade, Adriana Secatto, Roberto Nicolete, Camila Peres-Buzalaf, Simone Gusmão Ramos, Ruxana Sadikot, Claudia da Silva Bitencourt, Lúcia Helena Faccioli
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/950981
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author Priscilla Aparecida Tartari Pereira
Bruno Caetano Trindade
Adriana Secatto
Roberto Nicolete
Camila Peres-Buzalaf
Simone Gusmão Ramos
Ruxana Sadikot
Claudia da Silva Bitencourt
Lúcia Helena Faccioli
author_facet Priscilla Aparecida Tartari Pereira
Bruno Caetano Trindade
Adriana Secatto
Roberto Nicolete
Camila Peres-Buzalaf
Simone Gusmão Ramos
Ruxana Sadikot
Claudia da Silva Bitencourt
Lúcia Helena Faccioli
author_sort Priscilla Aparecida Tartari Pereira
collection DOAJ
description Prostaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum infection in C57BL/6 mice. Our results showed that treatment with celecoxib inhibited cyclooxygenase 2, reduced the total fungal burden, and reduced the concentration of PGE2, cytokines, lymphocytes, neutrophils, and mononuclear cells in the bronchoalveolar space and lung parenchyma. In addition, celecoxib treatment increased the synthesis of nitric oxide, IFN-γ, LTB4, and the phagocytic capacity of alveolar macrophages. Moreover, celecoxib treatment increased the survival of mice after infection with a lethal inoculum of H. capsulatum. These results suggest that prostaglandins alter the host immune response and play an important role in the pathogenesis of histoplasmosis. Thus, the inhibition of prostaglandins could be a valuable immunomodulatory strategy and antifungal therapy for histoplasmosis treatment.
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language English
publishDate 2013-01-01
publisher Wiley
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series Mediators of Inflammation
spelling doaj-art-c78a3c4c89a6450c952bca202718af142025-02-03T01:29:59ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/950981950981Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum InfectionPriscilla Aparecida Tartari Pereira0Bruno Caetano Trindade1Adriana Secatto2Roberto Nicolete3Camila Peres-Buzalaf4Simone Gusmão Ramos5Ruxana Sadikot6Claudia da Silva Bitencourt7Lúcia Helena Faccioli8Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilDepartamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, SP, BrazilUniversity of Florida, Gainesville, FL 32669, USADepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilDepartamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, 14040-903 Ribeirão Preto, SP, BrazilProstaglandins act as mediators of inflammation and, similar to cytokines, function as immune modulators during innate and adaptive immune responses. Therefore, using a pharmacological inhibitor, celecoxib, we investigated the role of prostaglandins in host defense against Histoplasma capsulatum infection in C57BL/6 mice. Our results showed that treatment with celecoxib inhibited cyclooxygenase 2, reduced the total fungal burden, and reduced the concentration of PGE2, cytokines, lymphocytes, neutrophils, and mononuclear cells in the bronchoalveolar space and lung parenchyma. In addition, celecoxib treatment increased the synthesis of nitric oxide, IFN-γ, LTB4, and the phagocytic capacity of alveolar macrophages. Moreover, celecoxib treatment increased the survival of mice after infection with a lethal inoculum of H. capsulatum. These results suggest that prostaglandins alter the host immune response and play an important role in the pathogenesis of histoplasmosis. Thus, the inhibition of prostaglandins could be a valuable immunomodulatory strategy and antifungal therapy for histoplasmosis treatment.http://dx.doi.org/10.1155/2013/950981
spellingShingle Priscilla Aparecida Tartari Pereira
Bruno Caetano Trindade
Adriana Secatto
Roberto Nicolete
Camila Peres-Buzalaf
Simone Gusmão Ramos
Ruxana Sadikot
Claudia da Silva Bitencourt
Lúcia Helena Faccioli
Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection
Mediators of Inflammation
title Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection
title_full Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection
title_fullStr Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection
title_full_unstemmed Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection
title_short Celecoxib Improves Host Defense through Prostaglandin Inhibition during Histoplasma capsulatum Infection
title_sort celecoxib improves host defense through prostaglandin inhibition during histoplasma capsulatum infection
url http://dx.doi.org/10.1155/2013/950981
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