Synthesis and anti-inflammatory effect of lipoxins in human airway epithelial cells.
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.
Bonnans
Caroline
C
Clinique des Maladies Respiratoires, INSERM U454-IFR 3, CHU-Montpellier, France.
Gras
Delphine
D
Chavis
Claude
C
Mainprice
Brigitte
B
Vachier
Isabelle
I
Godard
Philippe
P
Chanez
Pascal
P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007120:Immunochemistry; D016209:Interleukin-8 / Q000096:biosynthesis; D044045:Lipoxins / Q000096:biosynthesis* / Q000494:pharmacology; D044042:Receptors, Formyl Peptide / Q000096:biosynthesis; D044067:Receptors, Lipoxin / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; C105101:FPR2 protein, human; D006893:Hydroxyeicosatetraenoic Acids; D016209:Interleukin-8; D044045:Lipoxins; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; C048698:5,6-dihydroxy-7,9,11,14-eicosatetraenoic acid