Knockout of cytochrome P450 1A1 enhances lipopolysaccharide‐induced acute lung injury in mice by targeting NF‐κB activation

Abstract

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.

Keywords

• acute lung injury
• cytochrome P450 1A1
• LPS
• NF‐κB