title: IL-17A Monoclonal Antibody Partly Reverses the Glucocorticoids Insensitivity in Mice Exposed to Ozonec.
abstract: Exposure to ozone has been associated with airway inflammation and glucocorticoid insensitivity. This study aimed to observe the capacity of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) to reverse ozone-induced glucocorticoid insensitivity and to detect its effects with glucocorticoids in protecting against airway inflammation. After C57/BL6 mice were exposed to ozone (2.5 ppm; 3 h) for 12 times over 6 weeks, PBS, IL-17mAb (50 ug/ml), dexamethasone (2 mg/kg), and combination administration of IL-17mAb (50 ug/ml) and dexamethasone (2 mg/kg) were intraperitoneally injected into mice at a dose of 0.1 ml, respectively, for 10 times over 5 weeks. At sacrifice, lung histology, airway inflammatory cells, levels of related cytokines in bronchoalveolar lavage fluid (BALF), and serum were analyzed, airway inflammatory cell infiltration density and mean linear intercept (Lm) were measured, the expression of IL-17A mRNA, glucocorticoid receptors (GR), NF-κB, and p38 mitogen-activated protein kinase (MAPK) phosphorylation were determined. We found that combination administration markedly reduced ozone-induced total inflammatory cells, especially neutrophils; inhibited levels of cytokines, including IL-8, IL-17A, and TNF-α in BALF; and suppressed airway inflammatory cell infiltration density and Lm. Additionally, combination administration significantly elevated levels of IFN-γ in BALF, decreased the dexamethasone-induced increase of IL-17A mRNA, and increased the expression of GR and decrement of NF-κB and p38MAPK phosphorylation, which are also related to glucocorticoids insensitivity. Collectively, combination administration shows profound efficacy in inhibiting certain cytokines, and IL-17 mAb partly improved the glucocorticoids insensitivity via modulating the enhanced production rate and improving expression of IL-17A induced by glucocorticoids administration and p38MAPK, NF-κB signaling pathway.
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Fei
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Peng-Yu
authors.initials: PY
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Wu-Ping
authors.initials: WP
authors.lastname: Bao
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China. maggie_zhangmin@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, No. 100, Haining Road, Shanghai, 200080, China. xzhou53@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance / Q000187:drug effects; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010126:Ozone / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; C098680:Il17a protein, mouse; D020381:Interleukin-17; D016328:NF-kappa B; D010126:Ozone; D003907:Dexamethasone; D048051:p38 Mitogen-Activated Protein Kinases
keywords: airway inflammation; glucocorticoids insensitivity; interleukin-17A; ozone