Interleukin 22 attenuated angiotensin II induced acute lung injury through inhibiting the apoptosis of pulmonary microvascular endothelial cells.

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.

• Authors: Zhiyong Wu, Zhipeng Hu, Xin Cai, Wei Ren, Feifeng Dai, Huagang Liu, Jinxing Chang, Bowen Li
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 2210 (05 19 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28526849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Interleukins
• Proto-Oncogene Proteins c-bcl-2
• STAT3 Transcription Factor
• Angiotensin II

Topics

• Acute Lung Injury (etiology, metabolism, pathology)
• Angiotensin II (metabolism, pharmacology)
• Animals
• Apoptosis (drug effects)
• Biomarkers
• Cell Line
• Disease Models, Animal
• Endothelial Cells (metabolism)
• Gene Expression
• Humans
• Interleukins (metabolism, pharmacology)
• Male
• Mice
• Oxidation-Reduction
• Phosphorylation
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• STAT3 Transcription Factor (genetics, metabolism)
• Interleukin-22