title: Propofol attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production through p38 MAPK and SAPK/JNK in alveolar epithelial cells.
abstract: OBJECTIVE
  Propofol is widely used in sedation and surgical procedures involving patients with acute lung injury (ALI), a common complication in critically ill patients. Monocyte chemoattractant protein-1 (MCP-1) plays an important role in pathological changes in ALI. The present study investigated the anti-inflammatory effect and mechanism of propofol on MCP-1 production and mitogen-activated protein kinase (MAPK) phosphorylation induced by lipopolysaccharide (LPS) in alveolar epithelial cells (AECs).
  
  
  METHODS
  AECs were treated with 1 μg/ml LPS for 30 min, 1 h, 6 h, or 24 h following pretreatment with 12.5-100 μM propofol for 30 min. Cytokines and chemokines secretion were profiled using cytokine array, and mRNA and protein levels of MCP-1 were measured by RT-PCR and ELISA. The phosphorylation of p38 MAPK, p44/42 MAPK, SAPK/JNK, ATF-2, and c-Jun were measured by Western blot analysis.
  
  
  RESULTS
  Propofol at 50 and 100 μM dose-dependently inhibited MCP-1 mRNA expression (P < 0.05), and also propofol at 50 μM decreased extracellular MCP-1 protein levels (P < 0.05) compared to the LPS group. Propofol at 12.5-50 μM inhibited LPS-induced phosphorylation of p38 MAPK, p44/42 MAPK, SAPK/JNK, ATF-2, and c-Jun in AECs.
  
  
  CONCLUSIONS
  Propofol at clinically relevant concentrations attenuated LPS-induced MCP-1 mRNA expression and secretion by inhibiting the phosphorylation of p38 MAPK, SAPK/JNK, ATF-2, and c-Jun exerting its anti-inflammatory effects in AECs. These results suggest that propofol may modulate inflammatory response at clinically achievable concentrations in ALI.
authors.affiliation: Department of Anesthesiology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba, Japan. wlg5616854@msn.cn
authors.forename: Liguo
authors.initials: L
authors.lastname: Wei
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D015742:Propofol