Y Wang1, Y Zhang1, L Zhang1, M Li2, P Zhu1, W Ji1, R Liang1, L Qiin3, W Wu4, F Feng2, Y Jin1. 1. Department of epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China. 2. Department of Toxicology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China. 3. Institute of Chronic and Non-communicable Disease Prevention and Control, Henan Provincial Center for Disease Control and Prevention, Zhengzhou 450001, China. 4. Department of Occupational and Environmental Health, School of Public Health, Xinxiang Medical University, Xinxiang 453000, China.
Abstract
OBJECTIVE: To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice. METHODS: Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation. RESULTS: Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine. CONCLUSION: ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.
OBJECTIVE: To investigate the roles of angiotensin-converting enzyme 2 (ACE2) in ozone-induced pulmonary inflammation and airway remodeling in mice. METHODS: Sixteen wild-type (WT) C57BL/6J mice and 16 ACE2 knock-out (KO) mice were exposed to either filtered air or ozone (0.8 ppm) for 3 h per day for 5 consecutive days. Masson's staining and HE staining were used to observe lung pathologies. Bronchoalveolar lavage fluid (BALF) was collected and the total cell count was determined. The total proteins and cytokines in BALF were determined by BCA and ELISA method. The transcription levels of airway remodeling-related indicators in the lung tissues were detected using real-time quantitative PCR. The airway resistance of the mice was measured using a small animal ventilator with methacholine stimulation. RESULTS: Following ozoneexposure ACE2 KO mice had significantly higher lung pathological scores than WT mice (P < 0.05). Masson staining results showed that compared with ozone-exposed WT mice, ozone-exposed ACE2 KO mice presented with significantly larger area of collagen deposition in the bronchi [(19.62±3.16)% vs (6.49±1.34)%, P < 0.05] and alveoli [(21.63±3.78)% vs (4.44±0.99)%, P < 0.05]. The total cell count and total protein contents in the BALF were both higher in ozone-exposed ACE2 KO mice than in WT mice, but these differences were not statistically significant (P > 0.05). The concentrations of IL-6, IL-1β, TNF-α, CXCL1/KC and MCP-1 in the BALF were all higher in ozone-exposed ACE2 KO mice than in ozone-exposed WT mice, but only the difference in IL-1β was statistically significant (P < 0.05). The transcription levels of MMP-9, MMP-13, TIMP 4, COL1A1, and TGF-β in the lung tissues were all significantly higher in ozone-exposed ACE2 KO mice (P < 0.01). No significant difference was found in airway resistance between ozone-exposed ACE KO mice and WT mice after challenge with 0, 10, 25, or 100 mg/mL of methacholine. CONCLUSION: ACE2 participates in ozone-induced lung inflammation and airway remodeling in mice.
Authors: G J Rey-Parra; A Vadivel; L Coltan; A Hall; F Eaton; M Schuster; H Loibner; J M Penninger; Z Kassiri; G Y Oudit; B Thébaud Journal: J Mol Med (Berl) Date: 2012-01-14 Impact factor: 4.599
Authors: Shuiling Zhao; Anindya Ghosh; Chao-Sheng Lo; Isabelle Chenier; James W Scholey; Janos G Filep; Julie R Ingelfinger; Shao-Ling Zhang; John S D Chan Journal: Endocrinology Date: 2018-02-01 Impact factor: 4.736
Authors: Shehla S Razvi; Jeremy B Richards; Farhan Malik; Kevin R Cromar; Roger E Price; Cynthia S Bell; Tingting Weng; Constance L Atkins; Chantal Y Spencer; Katherine J Cockerill; Amy L Alexander; Michael R Blackburn; Joseph L Alcorn; Ikram U Haque; Richard A Johnston Journal: Am J Physiol Lung Cell Mol Physiol Date: 2015-09-18 Impact factor: 5.464
Authors: Milena Sokolowska; Valerie F J Quesniaux; Cezmi A Akdis; Kian Fan Chung; Bernhard Ryffel; Dieudonnée Togbe Journal: Front Immunol Date: 2019-09-13 Impact factor: 7.561
Authors: Yumiko Imai; Keiji Kuba; Shuan Rao; Yi Huan; Feng Guo; Bin Guan; Peng Yang; Renu Sarao; Teiji Wada; Howard Leong-Poi; Michael A Crackower; Akiyoshi Fukamizu; Chi-Chung Hui; Lutz Hein; Stefan Uhlig; Arthur S Slutsky; Chengyu Jiang; Josef M Penninger Journal: Nature Date: 2005-07-07 Impact factor: 49.962
Authors: Juan José Nieto-Fontarigo; Sofia Tillgren; Samuel Cerps; Asger Sverrild; Morten Hvidtfeldt; Sangeetha Ramu; Mandy Menzel; Adam Frederik Sander; Celeste Porsbjerg; Lena Uller Journal: Front Immunol Date: 2021-12-07 Impact factor: 7.561