Treatment of allergic airway inflammation and hyperrespon-siveness by imiquimod modulating transcrip

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Background 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-(, 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. Methods 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-( in bronchoalveolar lavage fluid (BALF) and serum were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of IL-4, IL-5, IFN-(, 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. Results 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. Conclusion 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. Background Recent advances in the development of Th1 / Th2 responses by inducing the production of Th1 cytokines like IFN- (, 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 investigchi whether imiquimod treatment inhibited airway inflammation by modulating transcription factors T- bet and GATA-3. Methods 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 The concentrations of IL-4, IL-5 and IFN- (in bronchoalveolar lavage fluid (BALF) and serum were The mRNA expressions of IL-4, IL-5, IFN- (T-bet and GATA-3 in lung and in CD4 + T cells were determined by reverse transcription polymerase chain reaction (RT Results It was demonstrated that imiquimod 1) attenuated OVA induced airway inflammation; 2) diminished the degree of airway hyperresponsiveness (AHR); 3) The protein expressions of T-bet and GATA-3 were measured by Western blot. 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. Conclusion 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 Thl phenotype.
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