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Relationship between Th17 cells infiltrated in lungs and pulmonary vascular reconstruction under hypobarric hypoxia
Authors:CUI Yu  GUAN Li-bin  LI Xiao-xu  YANG Cheng-zhong  TAN Xiao-ling  GAO Yu-qi  HUANG Jian
Institution:1. Department of High Altitude Physiology and High Altitude Biology, Third Military Medicine University, Chongqing 400038, China; 2. Department of High Altitude Special Procurement Medicine and High Altitude Special Procurement Equipment, Key Laboratory of High Altitude Medicine of Education Ministry, Key Laboratory of High Altitude Physiology and High Altitude Disease of PLA, College of High Altitude Military Medicine, Third Military Medicine University, Chongqing 400038, China
Abstract:AIM: To investigate the changes of retinoid-related orphan receptor γt(RORγt) mRNA and interleukin-17(IL-17) protein in the lung tissue under hypobaric hypoxia, and the relationship between Th17 cells and hypoxic pulmonary vascular reconstruction. METHODS: Male BALB/c mice(n=50) were randomly divided into control group and 3 d, 7 d, 14 d and 28 d hypobaric hypoxia groups. The mice in hypobaric hypoxia groups were housed in a hypobaric hypoxia chamber(simulated altitude of 6 000 m) for 3 d, 7 d, 14 d or 28 d. The mice in control group were housed in normal pressure and oxygen environment. The hemodynamic data were recorded by cardiac catheterization. The hypertrophy of right ventricle was evaluated by the ratio of weight of the right ventricle to the weight of the left ventricle plus interventri-cular septum, and the right ventricular weight over body weight. The spleen was collected and the proportions of the Th17(CD4+IL-17+RORγt+) cells were detected by flow cytometry. The serum levels of IL-4, IL-6 and IL-17 and the change of IL-17 in the lung tissue were measured by ELISA. The mRNA expression of RORγt in the spleen and lung tissues was measured by RT-qPCR. RESULTS: Compared with control group, the mouse right ventricular systolic pressure, the hypertrophy index of right ventricle and the serum IL-17 level were significantly elevated in hypoxia groups, which was consistent with the results of flow cytometry. The mRNA expression of RORγt in the lung tissue was also significantly increased in 7 d, 14 d and 28 d hypoxia groups. The expression of IL-17 in the lung tissue was significantly increased in 14 d and 28 d hypoxia groups. CONCLUSION: Hypoxia promotes differentiation of Th0 cells to Th17 cells in the spleen. The Th17 cells infiltrated in the lung tissue under hypobarric hypoxia are involved in pulmonary vascular reconstruction.
Keywords:Th17 cells  Retinoid-related orphan receptorγt  Interleukin-17  Hypoxic pulmonary hypertension  
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