Phosphorylation of signal transducer and activator of transcription 6 (STAT6) and STAT1, but not STAT3, induced by antigen inhalation in bronchial smooth muscles of sensitized mice.
The signal transducer and activator of transcription (STAT) family of molecules play a critical role in the signaling of many cytokines. In addition to STAT6, implication of STAT1 and STAT3 in the development of airway hyperresponsiveness (AHR) has also been suggested in allergic bronchial asthma. However, there is little information whether or not antigen challenge really causes the in vivo activation of these STAT molecules in bronchial smooth muscles (BSMs). In the present study, the activations of these STATs were examined in BSMs of mice with allergic bronchial asthma. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin (OA) antigen. Total protein samples of the left main bronchi were prepared at 3 after the last OA challenge, and Western blot analyses for total and tyrosine-phosphorylated STATs molecules were conducted. In addition to the phosphorylation of STAT6, a significant increase in the level of phosphorylated STAT1 was also observed after the antigen exposure. In contrast, no significant increase in the level of phosphorylated STAT3 was observed in this mouse model of allergic bronchial asthma. The antigen exposure did not change the protein expressions of these STATs themselves. These findings suggest that STAT6 and STAT1, but not STAT3, might be crucial signal transducers in the development of BSM hyperresponsiveness, one of the causes of AHR in asthmatics.
Chiba
Yoshihiko
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan. chiba@hoshi.ac.jp
Todoroki
Michiko
M
Misawa
Miwa
M
D000280:Administration, Inhalation; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects*; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009130:Muscle, Smooth / Q000187:drug effects*; D010047:Ovalbumin; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D000941:Antigens; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; D010047:Ovalbumin