title: Protective effects of luteolin against lipopolysaccharide-induced acute lung injury involves inhibition of MEK/ERK and PI3K/Akt pathways in neutrophils.
abstract: OBJECTIVE
  To investigate whether luteolin, the major polyphenolic components of Lonicera japonica, has beneficial effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to determine whether the protective mechanism involves anti-inflammatory effects on neutrophils.
  
  
  METHODS
  ALI was induced with intratracheal instillation of LPS in mice. The level of ALI was determined by measuring the cell count and protein content in bronchoalveolar lavage (BAL) fluid. Neutrophils were stimulated with formyl-Met-Leu-Phe (fMLP) or LPS in vitro. Chemotaxis and superoxide anion generation were measured to evaluate neutrophil activation. The potential involvement of intracellular signaling molecules in regulating neutrophil activation was analyzed by using Western blot.
  
  
  RESULTS
  LPS induced ALI in mice, as evidenced with leukocyte infiltration and protein leakage into the lungs. Luteolin attenuated LPS-induced leukocyte infiltration and protein extravasation. In cell studies, luteolin attenuated the fMLP-induced neutrophil chemotaxis and respiratory burst (IC(50) 0.2+/-0.1 micromol/L and 2.2+/-0.8 micromol/L, respectively), but had a negligible effect on superoxide anion generation during phorbol myristate acetate stimulation. Furthermore luteolin effectively blocked MAPK/ERK kinase 1/2 (MEK), extracellular signal-regulated kinase (ERK), and Akt phosphorylation in fMLP- and LPS-stimulated neutrophils.
  
  
  CONCLUSIONS
  These results indicate that luteolin has beneficial effects against LPS-induced ALI in mice, and the attenuation of neutrophil chemotaxis and respiratory burst by luteolin involves the blockade of MEK-, ERK-, and Akt-related signaling cascades.
authors.affiliation: Department of Neurosurgery, Da-Chien General Hospital, Miaoli, Taiwan, China.
authors.forename: Jen-pei
authors.initials: JP
authors.lastname: Lee
authors.forename: Yi-ching
authors.initials: YC
authors.lastname: Li
authors.forename: Hung-yi
authors.initials: HY
authors.lastname: Chen
authors.forename: Ruey-hseng
authors.initials: RH
authors.lastname: Lin
authors.forename: Shiang-suo
authors.initials: SS
authors.lastname: Huang
authors.forename: Hui-ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Pai-chuan
authors.initials: PC
authors.lastname: Kuan
authors.forename: Mao-fang
authors.initials: MF
authors.lastname: Liao
authors.forename: Chun-jung
authors.initials: CJ
authors.lastname: Chen
authors.forename: Yu-hsiang
authors.initials: YH
authors.lastname: Kuan
mesh_terms: D055371:Acute Lung Injury / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000633:toxicity; D031239:Lonicera / Q000737:chemistry; D047311:Luteolin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D047311:Luteolin