LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3

Abstract

G-protein-coupled receptors (GPCRs) transduce the signal of a wide variety of chemokines, cytokines, neurotransmitters, hormones, odorants, and others to regulate the biologic homeostasis, including hematopoiesis and immunity. Here we report the molecular cloning of leukocytespecific STAT-induced GPCR (LSSIG), which is a novel murine orphan GPCR with the highest homology to human GPR43. The mRNA expression of LSSIG was clearly induced in M1 leukemia cells during the leukemia inhibitory factor (LIF)-induced differentiation to macrophages, and the induction was evidently signal transducers and activators of transcription 3 (STAT3)-dependent. GPR43 expression was also strongly induced in HL-60 and U937 leukemia cells during the differentiation to monocytes. Further analysis showed that the expression of both LSSIG and GPR43 is highly restricted in hematopoietic tissues. Cytokine-stimulation induced LSSIG and GPR43 in bone marrow cells, and monocytes and neutrophils, respectively. These results suggest that LSSIG and GPR43 might play pivotal roles in differentiation and immune response of monocytes and granulocytes. (Blood.

Free Fatty Acid Receptors and Drug Discovery

“…GPR43 is also reported to be induced during the differentiation of leukocyte progenitor cells to monocytes or neutrophils and is found mainly in hematopoietic tissues, suggesting that GPR43 could have an important function in the differentiation and/or activation of leukocytes. 18) Karaki et al reported that GPR43 is expressed in peptide YY (PYY)-containing enteroendocrine cells and 5HT-containing mucosal mast cells, 19) which is consistent with physiologic data showing that shortchain FFAs stimulate the release of PYY 20) and serotonin 21) from the ileum and colon. Recently, Ge et al 14) have reported that adipocytes treated with acetate and propionate exhibit a reduction in lipolytic activity.…”

Urokinase-induced activation of the gp130/Tyk2/Stat3 pathway mediates a pro-inflammatory effect in human mesangial cells via expression of the anaphylatoxin C5a receptor

“…As no data on signaling pathways mediating C5aR expression are available, we asked whether the signal transducer and activator of transcription Stat3 might be one likely candidate. This transcription factor was recently shown to regulate expression of another G-protein-coupled receptor (Senga et al, 2003 Fig. 4B, Stat3 translocated efficiently into the nuclei of MCs stimulated with uPA.…”

Short-chain fatty acids act as antiinflammatory mediatorsby regulating prostaglandin E2 and cytokines

“…Interestingly, the murine ortholog of GPR43 was initially identified as leukocyte-specific STAT-induced GPCR (LSSIG). It was reported that expression of both murine LSSIG and human GPR43 is induced during the differentiation of leukocyte progenitor cells to monocytes or neutrophils, suggesting their involvement in leukocyte function and host defense [11] . SCFAs have long been known to modulate the immune response.…”