Involvement of integrin beta4 in ozone stress-induced airway hyperresponsiveness.
It is known that ozone stress can induce airway hyperresponsiveness (AHR). The underlying cellular and molecular mechanisms are not fully understood. We constructed a successive ozone-stressed rat model and showed that AHR caused by ozone stress presented as increased lung resistance (R(L)) to inhaled histamine but not baseline R(L). Meanwhile, structural disruption and decreased expression of integrin beta4 on airway epithelia were observed. Further regression analysis revealed a significant negative correlation between increases in R(L) to histamine (at 0.32 mg/ml) and mRNA expression of integrin beta4. Moreover, when integrin beta4 on human bronchial epithelial cells was knocked down, we found that reactive oxygen species was increased and apoptosis rates were higher. Overall, this study suggests that downregulation of integrin beta4 is important for the development ozone stress-induced AHR, presumably because it causes increased oxidative damage and epithelial apoptosis.
Liu
Chi
C
Physiology Department, Xiangya Medical School, Central South University, Changsha, Hunan, PR China.
Xiang
Yang
Y
Liu
Hui-jun
HJ
Gao
Ge
G
Howard
Susan T
ST
Zhu
Xiao-lin
XL
Qin
Xiao-qun
XQ
D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000403:Airway Resistance; D000818:Animals; D017209:Apoptosis; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D039663:Integrin beta4 / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018384:Oxidative Stress; D010126:Ozone / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D000393:Air Pollutants; D039663:Integrin beta4; D034741:RNA, Small Interfering; D010126:Ozone; D006632:Histamine