title: P38 mitogen-activated protein kinase inhibition attenuates pulmonary inflammatory response in a rat cardiopulmonary bypass model.
abstract: OBJECTIVE
  Cardiopulmonary bypass (CPB) produces an inflammatory response associated with pulmonary dysfunction. P38 mitogen-activated protein kinase (P38MAPK) have been shown to mediate pulmonary inflammatory response after CPB, we examined the effect of SB203580, a specific p38 MAPK inhibitor, on CPB-induced pulmonary inflammatory response.
  
  
  METHODS
  Sprague-Dawley rats (n=54) were randomized into three groups (each n=18): (1) S group, rats underwent sham CPB; (2) CPB group, rats underwent CPB; (3) SB group, rats underwent CPB plus pretreatment with SB203580 (10 mg/kg, i.v., 30 min before CPB). The lung samples were collected after 10 min, 60 min, and 150 min lung reperfusion (each n=6) in CPB group and SB group, and after 70 min, 120 min, and 210 min observation in S group as the control.
  
  
  RESULTS
  The level of lung phospho-IkappaBalpha, nuclear factor (NF)-kappaB activity and activating protein (AP)-1 activity in CPB group was increased than S group. CPB resulted in increased pulmonary tissue tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta expression and production, increased pulmonary inflammatory response. The in vivo administration of SB203580 prevented up-regulation of lung-phosphorylated p38 MAP kinase, decreased pulmonary tissue level of proinflammatory cytokines expression and production, and reduced lung inflammation.
  
  
  CONCLUSIONS
  These findings suggested that (1) p38 MAP kinase activation is one of the important aspects of the signaling event that mediate the release of TNF-alpha and IL-1beta and contributes to CPB-induced pulmonary inflammatory response, (2) SB203580 selectively inhibiting p38 MAP kinase activation efficaciously reduces pulmonary inflammatory response after CPB, and (3) p38 MAP kinase influence the activation of NF-kappaB in the lung during and after CPB.
authors.affiliation: Research Center for Congenital Heart Disease in FuWai Hospital, The Ministry of Health and Department of Cardiovascular Surgery, Cardiovascular Institute and FuWai Hospital, CAMS and PUMC, Beijing 100037, PR China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Du
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Cun Tao
authors.initials: CT
authors.lastname: Yu
authors.forename: Xiangming
authors.initials: X
authors.lastname: Fan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007093:Imidazoles / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011725:Pyridines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007375:Interleukin-1; D016328:NF-kappa B; D011725:Pyridines; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C093642:SB 203580