title: The protective effect of eupafolin against TNF-α-induced lung inflammation via the reduction of intercellular cell adhesion molecule-1 expression.
abstract: BACKGROUND
  Eupafolin, a major bioactive compound found in Phyla nodiflora, has the anti-inflammatory property. Upregulation of cell adhesion molecules in the lung airway epithelium is associated with the epithelium-leukocyte interaction and plays a critical role in the pathogenesis of lung airway inflammatory disorders. To investigate the effects of eupafolin on tumor necrosis factor-α (TNF-α)-induced intercellular cell adhesion molecule-1 (ICAM-1) expression in A549 human lung airway epithelial cells and the underlying mechanisms.
  
  
  METHODS
  The effect of eupafolin on ICAM-1 expression in A549 cells were examined by Western blotting and immunofluorescent staining. The mice were injected intraperitoneally with or without eupafolin and then were left untreated or were injected intratracheally with TNF-α. To detect the effect of eupafolin on ICAM-1 expression, the lung tissues were also examined by Western blotting and immunohistochemical staining.
  
  
  RESULTS
  Eupafolin pretreatment reduced the TNF-α-induced ICAM-1 expression and also the ERK1/2, JNK, p38, and AKT/PI3K phosphorylation. However, the increase in ICAM-1 expression with TNF-α treatment was unaffected by p38 and PI3K inhibitors. Eupafolin decreased the TNF-α-induced NF-κB p65 activation and its nuclear translocation. Furthermore, eupafolin reduced ICAM-1 expression in the lung tissues of TNF-α-treated mice.
  
  
  CONCLUSIONS
  Eupafolin exerts its anti-inflammatory activity by suppressing the TNF-α-induced ICAM-1 expression and subsequent monocyte adhesion via AKT/ERK1/2/JNK phosphorylation and nuclear translocation of NF-κB p65. These results suggest that eupafolin may represent a novel therapeutic agent targeting epithelial activation in lung inflammation.
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan; Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Hsin-Ching
authors.initials: HC
authors.lastname: Sung
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan; Center for Lipid and Glycomedicine Research (CLGR), Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Lipid Biosciences (CLB), Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Liang
authors.affiliation: Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Chiang-Wen
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of France and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Feng-Lin
authors.initials: FL
authors.lastname: Yen
authors.affiliation: Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Hsiao
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Jiang-Shieh
authors.affiliation: Department of Family Medicine and Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: jawshiun@ntu.edu.tw.
authors.forename: Jaw-Shiun
authors.initials: JS
authors.lastname: Tsai
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan. Electronic address: ylchenv@ntu.edu.tw.
authors.forename: Yuh-Lien
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D047309:Flavones / Q000302:isolation & purification / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000517:prevention & control*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D029648:Verbenaceae / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D047309:Flavones; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C503624:eupafolin
keywords: AKT; Eupafolin; Inflammation; Intercellular cell adhesion molecule-1; MAPKs