Differential regulation of monocytic expression of leukotriene and lipoxin receptors

Prostaglandins Other Lipid Mediat. 2015 Sep;121(Pt A):138-43. doi: 10.1016/j.prostaglandins.2015.07.005. Epub 2015 Aug 3.

Abstract

Introduction: Lipoxygenase pathway yields both pro-inflammatory leukotrienes and pro-resolving lipoxins. The aim of the present study was to determine the effects of T-lymphocytes and pro-inflammatory stimuli on the expression levels of the lipoxin FPR2/ALX receptor, and the leukotriene BLT1 receptor in monocytes and macrophages, and to characterize LXA4-induced effects on pro-inflammatory mediators.

Methods: Human macrophages were co-cultured with activated CD4(+) cells. THP-1 cells were stimulated with different cytokines, LXA4 and supernatant from activated CD4(+) cells. mRNA was extracted for qPCR experiments and protein was analyzed by flow cytometry.

Results: Co-culture of macrophages with activated CD4(+) cells or their supernatants up-regulated macrophage FPR2/ALX expression but did not alter BLT1 receptor expression. Monocyte stimulation with IFN-γ up-regulated FPR2/ALX mRNA and protein levels, whereas BLT1 mRNA was down-regulated. Finally, LXA4 decreased mRNA levels of MMP-9, CXCL16, IL-1β, and IL-8 in THP-1 cells.

Conclusion: The present study shows that pro-inflammatory stimuli lead to FPR2/ALX expression. LXA4 induces an anti-inflammatory response, which could participate in the resolution of inflammation.

Keywords: Eicosanoids; Inflammation; Leukotriene; Lipoxin; Lipoxygenase; Monocyte; Resolution of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Down-Regulation* / drug effects
  • Humans
  • Interferon-gamma / pharmacology
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Formyl Peptide / genetics*
  • Receptors, Leukotriene B4 / genetics*
  • Receptors, Lipoxin / genetics*
  • Up-Regulation* / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • FPR2 protein, human
  • HSH2D protein, human
  • LTB4R protein, human
  • RNA, Messenger
  • Receptors, Formyl Peptide
  • Receptors, Leukotriene B4
  • Receptors, Lipoxin
  • Interferon-gamma