Differential regulation of monocytic expression of leukotriene and lipoxin receptors.

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.

• Authors: Marcelo Heron Petri, Silke Thul, Olga Ovchinnikova, Magnus Bäck
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 121 Issue Pt A Pg. 138-43 (Sep 2015) ISSN: 1098-8823 [Print] United States
• PMID: 26248046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• 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

Topics

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