Interleucina-9 estimula a expressão de CCL17/TARC em células epiteliais de pulmão murino
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2012-08-03
Autores
Santos, Ariane Cristina Araujo dos [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Proposição: As células epiteliais das vias respiratórias desempenham uma importante função na patogênese da asma. Elas são responsáveis pela liberação de mediadores químicos ativadores do sistema imunológico na resposta inflamatória das vias aéreas. Citocinas e quimiocinas produzidas por leucócitos ativam as células estruturais dos brônquios e incitam a síntese de outros mediadores químicos que potencializam a inflamação no local. A interleucina-9 (IL-9) é uma importante citocina ativadora das células epiteliais, regula a produção de muco e induz a expressão de quimiocinas e citocinas. Os objetivos deste estudo foram investigar se células epiteliais de pulmão murino (LA-4) estimuladas com a citocina IL-9 produzem a quimiocina do timo regulada por ativação (CCL17/TARC) e o mediador lipídico leucotrieno-C4 (LTC4), e quais vias de sinalização intracelular estariam envolvidas nesse processo. Julga-se que as proteínas quinases desempenhem uma função primordial na expressão e ativação de citocinas e quimiocinas nas vias aéreas, portanto, foi investigada a função da p38 proteína quinase ativada por mitógeno (MAPK), MAPK p42/44, e fosfatidilinositol 3-quinase (PI3K) sobre o efeito da IL-9 na expressão da quimiocina CCL17/TARC em células LA-4. Abordagem experimental: a expressão de CCL17/TARC por LA-4 foi avaliada utilizando Reação em Cadeia da Polimerase Transcriptase Reversa (RT-PCR). A produção de leucotrieno C4 (LTC4) e CCL17/TARC foi avaliada por ELISA. As células LA-4 foram pré-tratados com o antagonista do receptor de cisteinil leucotrieno (CysLT) (MK 571) (10 μM), com o inibidor da p42/44 MAPK (PD98059) (30 μM), inibidor...
Background and propose: The airway epithelial cells play an important role in the pathogenesis of asthma, are responsible for the release of chemical mediators of the immune system triggers inflammation in the airways. Cytokines and chemokines produced by leukocytes activate structural bronchial cells and induce the synthesis of other chemical mediators which enhance the site inflammation. Interleukin-9 (IL-9) is an important cytokine activating epithelial cells, regulating mucus production and induces the expression of chemokines and cytokines. The objectives of this study were to investigate whether murine lung epithelial cells (LA-4) IL-9-stimulated produce the thymus and activation-regulated chemokines (CCL17/TARC) and lipid mediator leukotriene-C4 (LTC4) and what intracellular signaling pathways would be involved in this process. Kinases are believed to play a crucial role in the expression and activation of cytokines and chemokines in the airways. Therefore the role of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and phosphatidylinositol 3-kinase (PI3K) upon the effect of IL-9 on the CCL17/TARC expression in murine lung alveolar epithelial cells (LA-4) was investigated. Experimental approach: CCL17/TARC expression in LA-4 was evaluated using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Leukotriene C4 (LTC4) and CCL17/TARC production were assessed by ELISA. LA-4 had been pre-treated with cysteinyl leukotriene receptor antagonist (CysLT) (MK 571) (10 μM), p42/44 MAPK inhibitor (PD98059) (30 M), p38 MAPK inhibitor (SB203580) (30 M), and PI3K inhibitor (Wortmannin) (0.1 M) 30 min prior to IL-9 (40 ng.mL-1) stimulation. Key results: IL-9-stimulated LA-4 induced CCL17/TARC mRNA expression after 24 hours. PD98059 and...
Background and propose: The airway epithelial cells play an important role in the pathogenesis of asthma, are responsible for the release of chemical mediators of the immune system triggers inflammation in the airways. Cytokines and chemokines produced by leukocytes activate structural bronchial cells and induce the synthesis of other chemical mediators which enhance the site inflammation. Interleukin-9 (IL-9) is an important cytokine activating epithelial cells, regulating mucus production and induces the expression of chemokines and cytokines. The objectives of this study were to investigate whether murine lung epithelial cells (LA-4) IL-9-stimulated produce the thymus and activation-regulated chemokines (CCL17/TARC) and lipid mediator leukotriene-C4 (LTC4) and what intracellular signaling pathways would be involved in this process. Kinases are believed to play a crucial role in the expression and activation of cytokines and chemokines in the airways. Therefore the role of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and phosphatidylinositol 3-kinase (PI3K) upon the effect of IL-9 on the CCL17/TARC expression in murine lung alveolar epithelial cells (LA-4) was investigated. Experimental approach: CCL17/TARC expression in LA-4 was evaluated using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Leukotriene C4 (LTC4) and CCL17/TARC production were assessed by ELISA. LA-4 had been pre-treated with cysteinyl leukotriene receptor antagonist (CysLT) (MK 571) (10 μM), p42/44 MAPK inhibitor (PD98059) (30 M), p38 MAPK inhibitor (SB203580) (30 M), and PI3K inhibitor (Wortmannin) (0.1 M) 30 min prior to IL-9 (40 ng.mL-1) stimulation. Key results: IL-9-stimulated LA-4 induced CCL17/TARC mRNA expression after 24 hours. PD98059 and...
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Palavras-chave
Interleucina-9, Celulas epiteliais, Asma, Interleukin-9
Como citar
SANTOS, Ariane Cristina Araujo dos. Interleucina-9 estimula a expressão de CCL17/TARC em células epiteliais de pulmão murino. 2012. 64 f. Dissertação (mestrado) - Universidade Estadual Paulista Júlio de Mesquita Filho, Faculdade de Odontologia de Araçatuba , 2012.