Synthesis and anti-inflammatory effect of lipoxins in human airway epithelial cells

Biomed Pharmacother. 2007 Jun;61(5):261-7. doi: 10.1016/j.biopha.2007.02.016. Epub 2007 Mar 21.

Abstract

In this study, we investigated the synthesis of lipoxins (LXs) and their anti-inflammatory effects in different human airway epithelial cell culture models. After cell incubation with exogenous 5(S),6(R)-dihydroxy-7,9-trans-11,14-cis-eicosatetraenoic acid, LXA(4) was detected in supernatants of differentiated human bronchial epithelial cells by contrast to non-differentiated cells. Exogenous LXA(4) significantly inhibited tumor necrosis factor-alpha (TNF-alpha)-induced interleukin-8 (IL-8) release in the different epithelial cell types and the potency of inhibition was dependent of the accessibility of the specific LXA(4) receptor, formyl-peptide receptor like-1 (FPRL-1) expressed by all these cells. Immunohistochemistry analysis on human bronchial biopsies showed a high expression of FPRL-1 in the epithelium. Finally, an FPRL-1 receptor antagonist, boc-2 peptide reversed LXA(4) effect on IL-8 generation. Together, these findings indicate that differentiated human bronchial epithelium synthesizes LX in vivo which could have autocrine actions through its specific receptor FPRL-1 to promote resolution of airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Blotting, Western
  • Bronchi / cytology
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Humans
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • Immunochemistry
  • Interleukin-8 / biosynthesis
  • Lipoxins / biosynthesis*
  • Lipoxins / pharmacology
  • Receptors, Formyl Peptide / biosynthesis
  • Receptors, Lipoxin / biosynthesis
  • Respiratory Mucosa / cytology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • FPR2 protein, human
  • Hydroxyeicosatetraenoic Acids
  • Interleukin-8
  • Lipoxins
  • Receptors, Formyl Peptide
  • Receptors, Lipoxin
  • Tumor Necrosis Factor-alpha
  • lipoxin A4
  • 5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid