Knockout of cytochrome P450 1A1 enhances lipopolysaccharide‐induced acute lung injury in mice by targeting NF‐κB activation
Li‐xing Tian,
Xin Tang,
Wei Ma,
Jing Wang,
Wei Zhang,
Kuan Liu,
Tao Chen,
Jun‐yu Zhu,
Hua‐ping Liang
Affiliations
Li‐xing Tian
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Xin Tang
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Wei Ma
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Jing Wang
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Wei Zhang
Emergency and Trauma College Hainan Medical University Haikou China
Kuan Liu
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Tao Chen
Department of Intensive Care Unit the Affiliated Hospital of Zunyi Medical University Zunyi China
Jun‐yu Zhu
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Hua‐ping Liang
State Key Laboratory of Trauma, Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University Chongqing China
Acute lung injury (ALI) is accompanied by overactivation of multiple pro‐inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)‐induced ALI is unknown. In this study, CYP1A1 was shown to be upregulated in mouse lung in response to LPS. Using CYP1A1‐deficient (CYP1A1−/−) mice, we found that CYP1A1 knockout enhanced LPS‐induced ALI, as evidenced by increased TNF‐α, IL‐1β, IL‐6, and nitric oxide in lung; these effects were mediated by overactivation of NF‐κB and iNOS. Furthermore, we found that aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatinine levels were elevated in serum of LPS‐induced CYP1A1−/− mice. Altogether, these data provide novel insights into the involvement of CYP1A1 in LPS‐induced lung injury.
