A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils

Taisuke Ohira, Gerard Bannenberg, Makoto Arita, Minora Takahashi, Qingyuan Ge, Thomas E. Van Dyke, Gregory L. Stahl, Charles N. Serhan, John A. Badwey

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54 Citations (Scopus)

Abstract

Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A4 methyl ester, an aspirin-triggered lipoxin A4-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein 1, a downstream component of the p38-MAPK cascade in neutrophils, by mass spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM) also reduced phosphorylation/activation of several components of the p38-MAPK pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory effects, at least in part, by blocking activation of the p38-MAPK cascade in neutrophils, which is known to promote chemotaxis and other proinflammatory responses by these cells.

Original languageEnglish
Pages (from-to)2091-2098
Number of pages8
JournalJournal of Immunology
Volume173
Issue number3
DOIs
Publication statusPublished - 2004 Aug 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ohira, T., Bannenberg, G., Arita, M., Takahashi, M., Ge, Q., Van Dyke, T. E., Stahl, G. L., Serhan, C. N., & Badwey, J. A. (2004). A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils. Journal of Immunology, 173(3), 2091-2098. https://doi.org/10.4049/jimmunol.173.3.2091