title: Treatment of allergic airway inflammation and hyperresponsiveness by imiquimod modulating transcription factors T-bet and GATA-3.
abstract: 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-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.
  
  
  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-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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bian
authors.forename: Kai-sheng
authors.initials: KS
authors.lastname: Yin
authors.forename: Shu-xian
authors.initials: SX
authors.lastname: Jin
authors.forename: Xi-long
authors.initials: XL
authors.lastname: Zhang
authors.forename: Jin-yong
authors.initials: JY
authors.lastname: Zhou
authors.forename: Xiu-qin
authors.initials: XQ
authors.lastname: Ma
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: De
mesh_terms: D000280:Administration, Inhalation; D000634:Aminoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001980:Bronchi / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000502:physiology; D050990:GATA3 Transcription Factor / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D000077271:Imiquimod; D008168:Lung / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000235:genetics*; D000098815:T-bet Transcription Factor
chemical_list: D000634:Aminoquinolines; D016207:Cytokines; D050990:GATA3 Transcription Factor; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D010047:Ovalbumin; D000077271:Imiquimod