Proinflammatory Stimulants Promote the Expression of a Promiscuous G Protein-Coupled Receptor, mFPR2, in Microvascular Endothelial Cells

Abstract

Human formylpeptide receptor 2 (FPR2) and its mouse homologue mFPR2 belong to the G protein-coupled, seven-transmembrane receptor superfamily. Both FPR2 and mFPR2 recognize a variety of exogenous and host-derived chemotactic peptides associated with proinflammatory conditions. Since endothelial cells actively participate in inflammation, we investigated whether microvascular endothelial cells express mFPR2 and its regulation by proinflammatory factors. We found that resting primary mouse microvascular endothelial cells and a cell line bEnd.3 expressed low levels of mFPR2 at both mRNA and protein levels, which was markedly enhanced by two key proinflammatory stimulants, lipopolysaccharide (LPS) and interleukin (IL)-1β. While the inductive effect of LPS was dependent on the JNK MAP kinase, both JNK and ERK MAP kinases were utilized by IL-1β to enhance mFPR2 expression. Overexpression of dominant-negative IκBα attenuated LPS- and IL-1β-induced mFPR2 expression, indicating an essential role for NF-κB in regulating mFPR2 expression in endothelial cells by proinflammatory stimulants. Our results suggest that upregulated mFPR2 in vascular endothelial cells under inflammatory conditions may mediate cell responses in diseases in which mFPR2 agonists are elevated.

Lipoxin A4 Attenuates the Inflammatory Response in Stem Cells of the Apical Papilla via ALX/FPR2

“…We found that SCAP expressed a relatively low level of ALX/FPR2 in comparison with PBMC, however, this expression was upregulated by pro-inflammatory factors (TNF-α and LPS). These results are in line with other studies using microglial or endothelial cells 16 , 27 . Although no mechanistic studies have been performed at this point, we may hypothesize that ALX/FPR2 is upregulated through c-Jun N-Terminal protein kinase and transcription factor NF-κB signaling pathways as discussed in other studies 16 .…”

“…In this study, we identified for the first time that SCAP express the lipoxin receptor ALX/FPR2. The expression of ALX/FPR2 is upregulated by a variety of inflammatory stimulants such as TNF-α, interferon-γ as well as ligands for TLR-2, 3, 4, 7 and 9 in different cell types 15 , 16 . Although the effect was apparently weaker in comparison with microglial cells or microvascular endothelial cells, we demonstrated that important inflammatory mediators of pulpal and periapical diseases such as TNF-α and LPS upregulated ALX/FPR2 expression in SCAP.…”

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

“…The expression of FPRs is highest in sentinel innate cells with phagocytic or chemotactic activity such as neutrophils [13] , [14] , monocytes [13] , [15] , macrophages [15] , [16] and dendritic cells [15] , [17] . However, FPR are also expressed in non-phagocytic and “immobile” sentinel cells such as mucosal epithelial cells [18] , [19] , endothelial cells [20] – [22] and glia [23] – [25] . In these cells, FPRs exert a genuine “sentinel role” by sensing pathogens present in the microenvironment as well as by favouring repair upon damage and inflammation.…”

FPR2/ALX activation reverses LPS-induced vascular hyporeactivity in aorta and increases survival in a pneumosepsis model

“…In the present report it is shown that FPR2/ALX receptor is constitutively expressed in VSMC and that LPS increased its expression in both the cell line A7r5 and mouse aorta. So far, LPS has been shown to increase FPR2/ALX expression in microglia (Cui et al, 2002) and in microvascular endothelial cells (Mou et al, 2012).…”