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Aspirin‐triggered lipoxin A 4 and lipoxin A 4 up‐regulate transcriptional corepressor NAB1 in human neutrophils
Author(s) -
Qiu Fei-Hua,
Devchand Pallavi R.,
Wada Koichiro,
Serhan Charles N.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0576fje
Subject(s) - lipid signaling , lipoxin , microbiology and biotechnology , inflammation , receptor , chemistry , chemotaxis , signal transduction , transcriptional regulation , biology , gene expression , gene , biochemistry , immunology
Aspirin‐triggered 15‐epi‐lipoxin A 4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A 4 , a putative “stop signal” involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15‐ epi ‐16‐( para ‐fluoro)‐phenoxy‐lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti‐inflammatory actions. ATLa binds with high affinity to the lipoxin A 4 receptor, a G protein‐coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up‐regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B 4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid‐responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up‐regulation of NAB 1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa‐stimulated G protein‐coupled receptor pathway that is potentially protective and overlaps with the anti‐inflammatory glucocorticoid regulatory circuit.