Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-α secretion from human T cells

Amiram Ariel, Nan Chiang, Makoto Arita, Nicos A. Petasis, Charles N. Serhan

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Lipoxins (LX) and their aspirin-triggered 15-epimer endogenous isoforms are endogenous anti-inflammatory and pro-resolution eicosanoids. In this study, we examined the impact of LX and aspirin-triggered LXA4-stable analogs (ATLa) on human T cell functions. 15-epi-16-(p-fluoro)phenoxy-LXA4 (ATLa1) blocked the secretion of TNF-α from human PBMC after stimulation by anti-CD3 Abs, with the IC50 value of ≈0.05 nM. A similar action was also exerted by the native aspirin-triggered 15-epi-LXA4, a new 15-epi-16-(p-trifluoro)phenoxy-LXA4 analog (ATLa2), as well as LXB4, and its analog 5-(R/S)-methyl-LXB4. The LXA4 receptor (ALX) is expressed in peripheral blood T cells and mediates the inhibition of TNF-α secretion from activated T cells by ATLa1. This action was accomplished by inhibition of the anti-CD3-induced activation of extracellular signal-regulated kinase, which is essential for TNF-α secretion from anti-CD3-activated T cells. These results demonstrate novel roles for LX and aspirintriggered LX in the regulation of T cell-mediated responses relevant in inflammation and its resolution. Moreover, they provide potential counterregulatory signals in communication(s) between the innate and acquired immune systems.

Original languageEnglish
Pages (from-to)6266-6272
Number of pages7
JournalJournal of Immunology
Volume170
Issue number12
Publication statusPublished - 2003 Jun 15
Externally publishedYes

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Lipoxins
Extracellular Signal-Regulated MAP Kinases
Aspirin
T-Lymphocytes
Eicosanoids
Inhibitory Concentration 50
Immune System
Blood Cells
Protein Isoforms
Anti-Inflammatory Agents
Communication
lipoxin A4
lipoxin B4
Inflammation

ASJC Scopus subject areas

  • Immunology

Cite this

Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-α secretion from human T cells. / Ariel, Amiram; Chiang, Nan; Arita, Makoto; Petasis, Nicos A.; Serhan, Charles N.

In: Journal of Immunology, Vol. 170, No. 12, 15.06.2003, p. 6266-6272.

Research output: Contribution to journalArticle

Ariel, Amiram ; Chiang, Nan ; Arita, Makoto ; Petasis, Nicos A. ; Serhan, Charles N. / Aspirin-triggered lipoxin A4 and B4 analogs block extracellular signal-regulated kinase-dependent TNF-α secretion from human T cells. In: Journal of Immunology. 2003 ; Vol. 170, No. 12. pp. 6266-6272.
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