title: The PPARγ agonist, rosiglitazone, attenuates airway inflammation and remodeling via heme oxygenase-1 in murine model of asthma.
abstract: OBJECTIVE
  Rosiglitazone is one of the specific PPARγ agonists showing potential therapeutic effects in asthma. Though PPARγ activation was considered protective in inhibiting airway inflammation and remodeling in asthma, the specific mechanisms are still unclear. This study was aimed to investigate whether heme oxygenase-1 (HO-1) related pathways were involved in rosiglitazone-activated PPARγ signaling in asthma treatment.
  
  
  METHODS
  Asthma was induced in mice by multiple exposures to ovalbumin (OVA) in 8 weeks. Prior to every OVA challenge, the mice received rosiglitazone (5 mg/kg, p.o.). After the mice were sacrificed, the bronchoalveolar lavage fluid (BALF), blood samples and lungs were collected for analyses. The activities of HO-1, MMP-2 and MMP-9 in airway tissue were assessed, and the expression of PPARγ, HO-1 and p21 proteins was also examined.
  
  
  RESULTS
  Rosiglitazone administration significantly attenuated airway inflammation and remodeling in mice with OVA-induced asthma, which were evidenced by decreased counts of total cells, eosinophils and neutrophils, and decreased levels of IL-5 and IL-13 in BALF, and by decreased airway smooth muscle layer thickness and reduced airway collagen deposition. Furthermore, rosiglitazone administration significantly increased PPARγ, HO-1 and p21 expression and HO-1 activity, decreased MMP-2 and MMP-9 activities in airway tissue. All the therapeutic effects of rosiglitazone were significantly impaired by co-administration of the HO-1 inhibitor ZnPP.
  
  
  CONCLUSIONS
  Rosiglitazone effectively attenuates airway inflammation and remodeling in OVA-induced asthma of mice by activating PPARγ/HO-1 signaling pathway.
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Yan-ting
authors.initials: YT
authors.lastname: Zhu
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Gui-zuo
authors.initials: GZ
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Han
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: De-xin
authors.initials: DX
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Yong-hong
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Xin-ming
authors.initials: XM
authors.lastname: Xie
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Shao-jun
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Jia-mei
authors.initials: JM
authors.lastname: Lu
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Xiu-zhen
authors.initials: XZ
authors.lastname: Sun
authors.affiliation: Department of Respiratory Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shanxi 710004, China.
authors.forename: Man-xiang
authors.initials: MX
authors.lastname: Li
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D008565:Membrane Proteins; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse