Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3 / 中华医学杂志(英文版)
Tao BIAN; Kai-sheng YIN; Shu-xian JIN; Xi-long ZHANG; Jin-yong ZHOU; Xiu-qin MA; Jing-jing HU; Wei DE.
Chinese Medical Journal
; (24): 640-648, 2006.
Artículo
en Inglés
| WPRIM | ID: wpr-267070
<p><b>BACKGROUND</b>Imiquimod is an imidazoquinoline, which class of compounds are known to have antiviral and antitumoural properties. In recent studies, it was shown that imiquimod modulates the T helper cell type Th1/Th2 response by inducing the production of Th1 cytokines like IFN-gamma, and by inhibiting the Th2 cytokines like interleukin (IL)-4. Several investigators have shown that T-bet and GATA-3 are master Th1 and Th2 regulatory transcription factors. This study investigated whether imiquimod treatment inhibited airway inflammation by modulating transcription factors T-bet and GATA-3.</p><p><b>METHODS</b>Thirty-six male SD rats were randomly divided into a control group, an asthmatic group, and an imiquimod group, which was exposed to an aerosol of 0.15% imiquimod. Twenty-four hours after the last ovalbumin (OVA) challenge, airway responsiveness was measured and changes in airway histology were observed. The concentrations of IL-4, IL-5 and IFN-gamma in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5, IFN-gamma, T-bet and GATA-3 in lung and in CD4(+) T cells were determined by reverse transcription polymerase chain reaction (RT-PCR). The protein expressions of T-bet and GATA-3 were measured by Western blot.</p><p><b>RESULTS</b>It was demonstrated that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the degree of airway hyperresponsiveness (AHR); 3) decreased the Th2 type cytokines and increased Th1 type cytokines mRNA and protein levels; 4) modulated the Th1/Th2 reaction by inhibiting GATA-3 production and increasing T-bet production.</p><p><b>CONCLUSION</b>Imiquimod treatment inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in committing T helper cells to a Th1 phenotype.</p>
Asunto(s)
Animales Masculino Ratas Administración por Inhalación Aminoquinolinas Usos Terapéuticos Asma Quimioterapia Metabolismo Bronquios Patología Hiperreactividad Bronquial Quimioterapia Metabolismo Citocinas Eosinófilos Fisiología Factor de Transcripción GATA3 Genética Regulación de la Expresión Génica Pulmón Patología Ovalbúmina Alergia e Inmunología ARN Mensajero Ratas Sprague-Dawley Proteínas de Dominio T Box Factores de Transcripción Genética
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