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 re...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 Thl cytokines like IFN-γ, and by inhibiting the Th2 cytokines like interleukin （IL）-4. Several investigators have shown that T-bet and GATA-3 are master Thl and Th2 regulatory transcription factors. This study investigated whether irniquimod 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-γ in bronchoalveolar lavage fluid （BALF） and serum were measured by enzyme linked immunosorbent assay （ELISA）. The rnRNA expressions of IL-4, IL-5, IFN-γ, 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 ofT-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 Thl 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.展开更多
文摘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 Thl cytokines like IFN-γ, and by inhibiting the Th2 cytokines like interleukin （IL）-4. Several investigators have shown that T-bet and GATA-3 are master Thl and Th2 regulatory transcription factors. This study investigated whether irniquimod 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-γ in bronchoalveolar lavage fluid （BALF） and serum were measured by enzyme linked immunosorbent assay （ELISA）. The rnRNA expressions of IL-4, IL-5, IFN-γ, 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 ofT-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 Thl 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.
