Abstract
Apoptosis of pulmonary microvascular endothelial cells (PMVECs) was considered to be closely related to the pathogenesis of acute lung injury (ALI). We aim to investigate whether IL-22 plays protective roles in lung injury through inhibiting the apoptosis of PMVECs. ALI model was induced through subcutaneous infusion of angiotensin II (Ang II). Lung injury and infiltration of inflammatory cells were evaluated by determining the PaO2/FiO2, calculation of dry to weight ratio in lung, and immunohistochemisty analysis. Apoptosis of PMVECs was determined using TUNEL assay and flow cytometry, respectively. Immunofluorescence and Western blot analysis were used to determine the expression and localization of STAT3, as well as the nucleus transmission of STAT3 from cytoplasm after IL22 treatment. Pathological findings showed ALI was induced 1 week after AngII infusion. IL22 inhibited the AngII-induced ALI, attenuated the edema in lung and the infiltration of inflammatory cells. Also, it contributed to the apoptosis of PMVECs induced by AngII. Meanwhile, significant increase was noticed in the expression of STAT3, phosphorylation of Y705-STAT3, and migration from cytoplasm to the nucleus after IL-22 treatment (P < 0.05). The activation of STAT3 by IL22 showed significant attenuation after AG490 treatment. Our data indicated that IL22 showed protective effects on lung injury through inhibiting the AngII-induced PMVECs apoptosis and PMVEC barrier injury by activating the JAK2/STAT3 signaling pathway.
Highlights
Acute aortic dissection (AAD) is frequently reported to occur accompanied by acute lung injury (ALI) featured by severe oxygenation impairment in lung[1, 2]
A majority of AAD patients may present ALI featured by hypoxemia, which severely affects the outcome of the patients
Our previous study showed angiotensin II (Ang II)-induced pulmonary microvascular endothelial cells (PMVECs) apoptosis was closely related to the pathogenesis of AAD complicated with ALI3
Summary
Acute aortic dissection (AAD) is frequently reported to occur accompanied by acute lung injury (ALI) featured by severe oxygenation impairment in lung[1, 2]. Our previous study reported elevation of Angiotensin II (Ang II) in AAD patients, especially those combined with ALI. In these patients, Ang II induced pulmonary microvascular endothelial cells (PMVECs) apoptosis, which subsequently resulted in interruption of the integrity of the PMVEC barrier[3]. The viability, activation and angiogenesis of human umbilical vein endothelial cells (HUVECs)[14] On this basis, we speculated that IL-22 may involve in the anti-apoptosis of PMVECs, which may be related to the protective effects in lung. Mice ALI model was established through subcutaneous injection of AngII, and the roles of IL-22 in the lung injury and the PMVEC barrier were investigated. IL-22 was used to treat the cultured PMVECs to investigate its roles in the anti-apoptosis of PMVECs
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