Marcelo Heron Petri1, Silke Thul2, Olga Ovchinnikova2, Magnus Bäck2. 1. Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden. Electronic address: marcelo.petri@ki.se. 2. Department of Medicine, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
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.
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.