FAM19A4 is a novel cytokine ligand of formyl peptide receptor 1 (FPR1) and is able to promote the migration and phagocytosis of macrophages

Abstract

FAM19A4 is an abbreviation for family with sequence similarity 19 (chemokine (C-C motif)-like) member A4, which is a secretory protein expressed in low levels in normal tissues. The biological functions of FAM19A4 remain to be determined, and its potential receptor(s) is unclarified. In this study, we demonstrated that FAM19A4 was a classical secretory protein and we verified for the first time that its mature protein is composed of 95 amino acids. We found that the expression of this novel cytokine was upregulated in lipopolysaccharide (LPS)-stimulated monocytes and macrophages and was typically in polarized M1. FAM19A4 shows chemotactic activities on macrophages and enhances the macrophage phagocytosis of zymosan both in vitro and in vivo with noticeable increases of the phosphorylation of protein kinase B (Akt). FAM19A4 can also increase the release of reactive oxygen species (ROS) upon zymosan stimulation. Furthermore, based on receptor internalization, radio ligand binding assays and receptor blockage, we demonstrated for the first time that FAM19A4 is a novel ligand of formyl peptide receptor 1 (FPR1). The above data indicate that upon inflammatory stimulation, monocyte/macrophage-derived FAM19A4 may play a crucial role in the migration and activation of macrophages during pathogenic infections.

Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice

“…Specifically, many cytokines show bell-shaped dose-response curves with optima at low concentrations. 30 This result was also consistent with the results of our previous study, in which we found that 4 ng/ml rhCTRP4 was more effective than 40 ng/ml rhCTRP4 in HepG2 cells. 8 Figure 3 The production of pro-inflammatory cytokines and the infiltration of macrophages in the colons of the CTRP4-tg mice were decreased after DSS treatment.…”

Identification of FAM3D as a novel endogenous chemotaxis agonist for the FPRs (formyl peptide receptors)

“…FPR1 and FPR2 are mainly expressed in neutrophils and monocytes, and they have been known to transduce proinflammatory (Karlsson et al, 2009;Partida-Sanchez et al, 2004) as well as anti-inflammatory signals (Herrera et al, 2015;Wang et al, 2015). During a response to infection, accumulation and activation of neutrophil granulocytes at inflammatory sites are of profound importance (Bidula et al, 2015).…”

“…During a response to infection, accumulation and activation of neutrophil granulocytes at inflammatory sites are of profound importance (Bidula et al, 2015). FPR-related signaling pathways, including MAPK (Hazeldine et al, 2015), PI3K-AKT (Wang et al, 2015), and JAK-STAT-SOCS (Pupjalis et al, 2011) pathways in neutrophils or macrophages, participate in the proliferation, metastasis and/or survival of these leukocytes. Our results indicate that FAM3D activates ERK1/2 and p38 MAPK proteins in neutrophils through FPR1 or FPR2.…”

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

“…Significant chemotaxis was compared with medium and was defined as the chemotactic index .2.0. In the cross-desensitization chemotaxis assays, CCL2 and CYTL1 were tested for their abilities to chemoattract CCR2B-expressing HEK293 cells, monocytes, or macrophages with or without CCL2 or CYTL1 pretreatment for 1 h, and the chemotaxis index was calculated (6,23).…”

“…To find novel potential cytokines, we established an immunogenomics-based screening platform, as previously reported (5). Several secreted proteins with important functions have been identified (6)(7)(8), among which is cytokine-like 1 (CYTL1).…”