MicroRNA-181b Regulates ALX/FPR2 Receptor Expression and Proresolution Signaling in Human Macrophages

Abstract

Background:The ALX/FPR2 receptor recognizes the proresolution mediators lipoxin A 4 (LXA 4 ) and resolvin (Rv) D1, thus modulating immune responses. Results: miR-181b binds to the 3Ј-UTR of the ALX/FPR2 gene, regulating its expression. mir-181b blunted LXA 4 -and RvD1-induced macrophage phagocytosis. Conclusion: miR-181b controls ALX/FPR2 expression. This mechanism modulates proresolution signals in macrophages. Significance: miR regulation of ALX/FPR2 expression may be exploited for innovative anti-inflammatory strategies.

Differential regulation of monocytic expression of leukotriene and lipoxin receptors

“…The first promoter, which yielded a longer mRNA, did not translate into protein in macrophages [21]. In contrast, studies about microRNAs (miR), more specifically miR-181b, described that this particular miR directly targets FPR2/ALX mRNA and reduces both FPR2/ALX mRNA and protein [26]. Taken together with those previous reports, the present results (Fig 1 and 2) confirm that FPR2/ALX expression is highly regulated at transcriptional and translational level and that increased mRNA expression partly translates into increased protein levels.…”

Specialised lipid mediators and their targets

“…Exogenous introduction of LXA4 in Fpr2/3 +/+ mice attenuates IRI induced inflammation, while this effect is lost in Fpr2/3 −/− mice [75]. Recently Pierdomenico et al [77] revealed a novel regulatory system of FPR2/ALX expression by microRNA (miR). The authors demonstrate within monocytes differentiating to macrophages miR-181b expression declines accompanied by an increase in FPR2LAX expression, while overexpressing miR181b down-regulated FPR2/ALX expression and attenuated LXA4 stimulated phagocytosis [77].…”

“…Recently Pierdomenico et al [77] revealed a novel regulatory system of FPR2/ALX expression by microRNA (miR). The authors demonstrate within monocytes differentiating to macrophages miR-181b expression declines accompanied by an increase in FPR2LAX expression, while overexpressing miR181b down-regulated FPR2/ALX expression and attenuated LXA4 stimulated phagocytosis [77]. The consequences of unresolved inflammation are scarring, fibrosis and eventual organ failure.…”

N-3 PUFAs and neuroinflammatory processes in cognitive disorders

“…Indeed, RvD1 activates lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2) and orphan receptor G protein coupling receptor 32 (GPR32) to limit leukocyte infiltration in tissues and attenuate the production of proinflammatory cytokines (Fredman et al, 2014;Wang et al, 2014). Interestingly, RvD1 promotes the synthesis of pro-resolvin miRNAs and elicits macrophage polarization toward an M2-like phenotype (Pierdomenico et al, 2015). LC PUFA cannot be synthesized by vertebrates and must be obtained from diet.…”