Aspirin-triggered lipoxin A4 attenuates lipopolysaccharide-induced acute lung injury by inhibiting activation of mitogen-activated protein kinases and NF-κB in mice.
Despite advances in patient care, effective approaches to acute lung injury (ALI), are currently unceratin. Aspirin-triggered lipoxin A4 (ATL), an endogenous lipid mediator, has been found to have potent anti-inflammatory and pro-resolving effects. In this study, we found ATL exerted protective effects on LPS-induced ALI in mice through inhibiting activations of MAPKs and NF-κB. Our findings revealed that pretreatment by ATL alleviated lung histopathologic changes and injury scores, and reduced leukocytes and protein concentration in the bronchoalveolar lavage fluid (BALF). We further found down-regulation of pulmonary myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein (MCP)-1, and up-regulation of interleukin-10 levels after treatment with ATL in a dose-dependent manner. Moreover, ATL blocked phosphorylations of p38 MAPK, ERK1/2 and JNK, activation of NF-κB, and DNA-binding activity of activator protein-1 (AP-1) and NF-κB in the lung tissues of LPS-challenged mice. Our study suggested that the anti-inflammatory effects of ATL on LPS-induced ALI in mice were at least partly correlated with inhibited activations of mitogen-activated protein kinases and NF-κB.
['Liu|Mei|M|', 'Chen|Shibiao|S|', 'Shang|You|Y|', 'Yao|Shanglong|S|']
Aspirin-triggered lipoxin A4 acute lung injury mitogen-activated protein kinases NF-κB lipopolysaccharide