title: Inhalation of progesterone inhibits chronic airway inflammation of mice exposed to ozone.
abstract: Chronic ozone exposure leads to a model of mice with lung inflammation, emphysema and oxidative stress. Progesterone plays an important role in attenuating the neuroinflammation. We assume that progesterone will reduce the chronic airway inflammation exposed to ozone and evaluate whether combination of progesterone with glucocorticoids results in synergistic effects. C57/BL6 mice were exposed to ozone (2.5ppm, 3h) 12 times over 6 weeks, and were administered with progesterone (0.03 or 0.3mg/L; inhaled) alone or combined with budesonide (BUD) (0.2g/L) after each exposure until the tenth week. Mice were studied 24h after final exposure, cells and inflammatory mediators were assessed in bronchoalveolar lavage fluid (BALF) and lungs used for evaluation of glucocorticoids receptors (GR), p38 mitogen-activated protein kinase (MAPK) phosphorylation and nuclear transcription factor κB (NF-κB) activation. Exposure to ozone resulted in a marked lung neutrophilia. Moreover, in ozone-exposed group, the levels of oxidative stress-related interleukin (IL)-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, airway inflammatory cells infiltration density, mean linear intercept (Lm) were greatly increased, FEV25and glucocorticoids receptors (GR) were markedly decreased. Comparable to BUD, progesterone treatment dose-dependently led to a significant reduction of IL-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, and an increase of FEV25and GR. Progesterone combined with BUD resulted in dramatic changes, compared to monotherapy of BUD or progesterone. Therefore, these results demonstrate that chronic ozone exposure has profound airway inflammatory effects counteracted by progesterone and progesterone acts synergistically with glucocorticoids in attenuating the airway inflammation dose-dependently.
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: Wuping
authors.initials: W
authors.lastname: Bao
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China. Electronic address: maggie_zhangmin@163.com.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015153:Blotting, Western; D019819:Budesonide / Q000008:administration & dosage; D002908:Chronic Disease; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000008:administration & dosage; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D011374:Progesterone / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000139:chemically induced* / Q000473:pathology
chemical_list: D005938:Glucocorticoids; D011374:Progesterone; D019819:Budesonide; D010126:Ozone
keywords: Airway inflammation; Budesonide; NF-κB; Ozone; Progesterone; p38MAPK