Antigen exposure causes activations of signal transducer and activator of transcription 6 (STAT6) and STAT1, but not STAT3, in lungs 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 pathogenesis of allergic airway diseases has also been suggested. However, there is little information whether or not antigen challenge to sensitized animals causes the in vivo activation of STAT1 and/or STAT3 in the airways. In the present study, the activations of these STAT molecules were monitored in lungs of mice with allergic bronchial asthma. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin (OA) antigen. Total protein samples of lungs were prepared at ∼1-24 h after the last OA challenge, and western blot analyses for total and tyrosine-phosphorylated STATs (pSTATs) molecules were conducted. In addition to the phosphorylation of STAT6, STAT1 was also phosphorylated in lungs after the inhalation of OA antigen. Both the phosphorylation of STAT6 and STAT1 occurred at the early stage after the antigen exposure. In contrast, no significant increase in the level of pSTAT3 was observed in this mouse model of allergic bronchial asthma. In conclusion, the current findings suggest that STAT6 and STAT1, but not STAT3, might be crucial signal transducers in the pathogenesis of allergic bronchial asthma.
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan. chiba@hoshi.ac.jp
Yoshihiko
Y
Chiba
Michiko
M
Todoroki
Miwa
M
Misawa
D000818:Animals; D000941:Antigens / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation; D050794:STAT1 Transcription Factor / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor / Q000096:biosynthesis*; D050800:STAT6 Transcription Factor / Q000096:biosynthesis*; D013997:Time Factors
D000941:Antigens; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; C494100:Stat6 protein, mouse; D010047:Ovalbumin