title: Activation of p38 mitogen-activated protein kinase in ovalbumin and ozone-induced mouse model of asthma.
abstract: OBJECTIVE
  Ozone exposure worsens the development of allergen-induced asthma. The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in the development of the inflammatory response, airway hyperresponsiveness (AHR) and airway remodelling. In this study, the role of the p38 MAPK pathway on the effects of chronic ozone exposure in ovalbumin (OVA)-sensitized and -challenged mice was investigated.
  
  
  METHODS
  Mice were sensitized and challenged with OVA followed by ozone exposure. Dexamethasone (Dex) and SB239063, a p38 MAPK inhibitor, were used as preventive treatment.
  
  
  RESULTS
  Compared with OVA-challenged mice, ozone exposure of OVA-challenged mice led to enhanced recruitment of inflammatory cells in bronchoalveolar lavage fluid, increases in inflammation scores, collagen accumulation, bronchial wall thickness and messenger RNA levels of inflammatory cytokines, along with activation of p38 MAPK/HSP27 and downregulation of MAPK phosphatase-1 (MKP-1) in the lung tissue. Dex treatment partially attenuated lung inflammation, while the cotreatment of Dex and SB239063 effectively reduced lung inflammation, inhibited airway remodelling, inactivated p38 MAPK/HSP27 and upregulated MKP-1 in the lung tissue.
  
  
  CONCLUSIONS
  Ozone exposure aggravated airway inflammation, airway remodelling, activation of p38 MAPK and downregulation of MKP-1 in OVA-sensitized and -challenged mice, which was ineffectively controlled by corticosteroids. p38 MAPK activation is a likely pathway involved in corticosteroid insensitivity.
authors.affiliation: Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Aihua
authors.initials: A
authors.lastname: Bao
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D054638:Dual Specificity Phosphatase 1 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000009:adverse effects*; D010126:Ozone / Q000009:adverse effects*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*
chemical_list: D000305:Adrenal Cortex Hormones; D004791:Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D007093:Imidazoles; D011743:Pyrimidines; D010126:Ozone; D010047:Ovalbumin; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; C406525:SB 239063
keywords: asthma; glucocorticoid; ozone; p38 mitogen-activated protein kinase