interleukin-8 and 5-6-dihydroxy-7-9-11-14-eicosatetraenoic-acid

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.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Bronchi; Cells, Cultured; Chromatography, High Pressure Liquid; Epithelial Cells; Humans; Hydroxyeicosatetraenoic Acids; Immunochemistry; Interleukin-8; Lipoxins; Receptors, Formyl Peptide; Receptors, Lipoxin; Respiratory Mucosa; Tumor Necrosis Factor-alpha