title: Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice.
abstract: Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Peng-Yu
authors.initials: PY
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wu-Ping
authors.initials: WP
authors.lastname: Bao
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: xzhou53@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D004646:Emphysema / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010126:Ozone; D011014:Pneumonia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D016207:Cytokines; D020381:Interleukin-17; D012333:RNA, Messenger; D010126:Ozone
keywords: Airway inflammation; Antibody; IL-17A; Ozone