Lipoxin A4 attenuates LPS-induced acute lung injury via activation of the ACE2-Ang-(1-7)-Mas axis

QF Chen, XD Kuang, QF Yuan, H Hao… - Innate …, 2018 - journals.sagepub.com
QF Chen, XD Kuang, QF Yuan, H Hao, T Zhang, YH Huang, XY Zhou
Innate immunity, 2018journals.sagepub.com
Previous studies have reported that lipoxin A4 (LXA4) and the angiotensin I-converting
enzyme 2 (ACE2), angiotensin-(1-7)[Ang-(1-7)], and its receptor Mas [ACE2-Ang-(1-7)-Mas]
axis play important protective roles in acute lung injury (ALI). However, there is still no direct
evidence of LXA4-mediated protection via the ACE2-Ang-(1-7)-Mas axis during ALI. This
work was performed using an LPS-induced ALI mouse model and the data indicated the
following. First, the animal model was established successfully and LXA4 ameliorated LPS …
Previous studies have reported that lipoxin A4 (LXA4) and the angiotensin I-converting enzyme 2 (ACE2), angiotensin-(1-7) [Ang-(1-7)], and its receptor Mas [ACE2-Ang-(1-7)-Mas] axis play important protective roles in acute lung injury (ALI). However, there is still no direct evidence of LXA4-mediated protection via the ACE2-Ang-(1-7)-Mas axis during ALI. This work was performed using an LPS-induced ALI mouse model and the data indicated the following. First, the animal model was established successfully and LXA4 ameliorated LPS-induced ALI. Second, LXA4 could increase the concentration and activity of ACE2 and the levels of Ang-(1-7) and Mas markedly. Third, LXA4 decreased the levels of TNF-α, IL-1β, and reactive oxygen species while increasing IL-10 levels. Fourth, LXA4 inhibited the activation of the NF-κB signal pathway and repressed the degradation of inhibitor of NF-κB, the phosphorylation of NF-κB, and the translocation of NF-κB. Finally, and more importantly, BOC-2 (LXA4 receptor inhibitor), MLN-4760 (ACE2 inhibitor), and A779 (Mas receptor antagonist) were found to reverse all of the effects of LXA4. Our data provide evidence that LXA4 protects the lung from ALI through regulation of the ACE2-Ang-(1-7)-Mas axis.
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