Expression and Signaling of Formyl-Peptide Receptors in the Brain

Abstract

The human formyl-peptide receptor (FPR) and its variants FPRL1 and FPRL2 belong to the G-protein coupled seven transmembrane receptor (GPCR) family sensitive to pertussis toxin. FPR and FPRL1 were first detected in phagocytic leukocytes, and FPRL2 was found in monocytes and in dendritic cells. The three receptors were subsequently identified in other cell types or tissues, including neuronal cells and brain, where FPR and FPRL1 play a key role in angiogenesis, cell proliferation, protection against and cell death, as well as in neuroendocrine functions. Binding of different agonists to FPRs triggers several signaling pathways, activates NFkB and STAT3 transcriptional factors and induces the accumulation of the CDK inhibitors p21(waf1/cip1), p16(INK4) and p27(kip1). Signaling molecules, such as ERKs, JNK, PKC, p38MAPK, PLC and PLD are involved in these intracellular cascades. In this article we briefly review FPRs expression and signaling in neuronal cells.

Lack of formyl peptide receptor 1 and 2 leads to more severe inflammation and higher mortality in mice with of pneumococcal meningitis

“…Fpr1 encodes murine Fpr1, which is considered the murine orthologue of human FPR, whereas Fpr-rs2 (mFPR2) encodes a receptor that is most similar to human formyl peptide receptor like 1 (FPRL1) or FPR2. 10,11 It is known that the receptor interacts with a menagerie of structurally diverse ligands including some from bacterial origins beside fMLF, such as Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), derived from Helicobacter pylori, HIV envelope peptides, or is associated with different neurodegenerative disorders, including Alzheimer's and prion disease. 12 Previous works revealed the expression of FPRs in the brain by glial cells.…”

“…12 Previous works revealed the expression of FPRs in the brain by glial cells. 13,14 In addition, the receptors are important for the chemotatic movement and mobilization of neutrophils, and FPRdeficient mice showed an impaired antibacterial host defence against Listeria monocytogenes infection. 15,16 Furthermore, a recent work revealed involvement of FPRL1 (FPR2) in the inflammatory response of glial cells after bacterial exposure.…”

“…The formyl peptide receptors are chemotactic G-protein coupled receptors for the bacterial cell wall component fMLF. 14 To analyse whether the deficiency of FPRs resulted in compensatory reactions of other chemotactic agents, we revealed the mRNA expression of CCL2, which recruits monocytes, memory T cells and dendritic cells to the sites of inflammation, 35 and CCL3, which is involved in the acute inflammatory state in the recruitment and activation of polymorphonuclear leucocytes. 36 CCL2 expression was significantly increased in both the hippocampal formation as well as the frontal cortex of FPR1-deficient mice only (12 664 AE 4734-fold and 616 AE 132-fold An asterisk indicates a significant difference between infected WT and infected FPR1-KO or FPR2-KO mice as determined by ANOVA followed by Bonferroni test (*P < 0Á05; **P < 0Á01; ***P < 0Á001).…”

Deficiency of Formyl Peptide Receptor 1 and 2 Is Associated with Increased Inflammation and Enhanced Liver Injury after LPS-Stimulation

“…The second member of the FPR-Family, FPR2, also known as FPRL1/LipoxinA4-receptor is poorly chemotatic and only high concentrations of fMLF induce its signalling regarding to this PAMP [18]. Furthermore the signalling of both receptors is highly various and depends on the receptor-ligand interaction [19]. The role of bacterial translocation in liver diseases has changed in the last years.…”

Estrogen Receptor Alpha 36 Gene Knockdown Promote the Expression of NF-κB in PC12 Cells

“…Activated (NF-κB) controls the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways, such as synaptic plasticity, cell injury, and the adjustment of the immune and inflammatory response factors expressions, such as cell adhesion molecules and cytokines. In the central nervous system, NF-κB controls inflammatory reactions and the apoptotic cell death following nerve injury [1], which plays a regulating role in the course of inflammation and immunoreaction during neuron apoptosis and neurodegenerative diseases and the change of NF-κB expression caused the neuron death and astrocyte activation. It is also reported that the activation of NF-κB and CREB is involved in the protection of chromaffin cells and the sympathoadrenal PC12 cells (an established model for the study of neuronal cell apoptosis and survival) against serum deprivation-induced apoptosis by the neuroactive steroids dehydroepiandrosterone (DHEA), its sulfate ester DHEAS and allopregnanolone (Allo) [2].…”