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Chin. med. j ; Chin. med. j;(24): 640-648, 2006.
Article de Anglais | WPRIM | ID: wpr-267070

RÉSUMÉ

<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>


Sujet(s)
Animaux , Mâle , Rats , Administration par inhalation , Aminoquinoléines , Utilisations thérapeutiques , Asthme , Traitement médicamenteux , Métabolisme , Bronches , Anatomopathologie , Hyperréactivité bronchique , Traitement médicamenteux , Métabolisme , Cytokines , Granulocytes éosinophiles , Physiologie , Facteur de transcription GATA-3 , Génétique , Régulation de l'expression des gènes , Poumon , Anatomopathologie , Ovalbumine , Allergie et immunologie , ARN messager , Rat Sprague-Dawley , Protéines à domaine boîte-T , Facteurs de transcription , Génétique
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