Prostaglandin E2 transactivates the colony-stimulating factor-1 receptor and synergizes with colony-stimulating factor-1 in the induction of macrophage migration via the mitogen-activated protein kinase ERK1/2

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Graziana DigiacomoElisabetta Rovida

Abstract

Prostaglandin E2 (PGE2), a key mediator of immunity, inflammation, and cancer, acts through 4 G-protein-coupled E-prostanoid receptors (EPs 1-4). Crosstalk between EPs and receptor tyrosine kinases also occurs. Colony-stimulating factor-1 receptor (CSF-1R) is an RTK that sustains the survival, proliferation, and motility of monocytes/macrophages, which are an essential component of innate immunity and cancer development. The aim of this study was to investigate on a possible crosstalk between EP and CSF-1R. In BAC1.2F5 and RAW264.7 murine macrophages, CSF-1 (EC₅₀ = 18.1 and 10.2 ng/ml, respectively) and PGE2 (EC₅₀ = 1.5 and 5.5 nM, respectively) promoted migration. PGE2 induced rapid CSF-1R phosphorylation that was dependent on Src family kinases (SFKs). CSF-1R inhibition reduced PGE2-elicited ERK1/2 phosphorylation and macrophage migration, indicating that CSF-1R plays a role in PGE2-mediated immunoregulation. EP4 appeared responsible for functional PGE2/CSF-1R crosstalk. Furthermore, PGE2 synergized with CSF-1 in inducing ERK1/2 phosphorylation and macrophage migration. ERK1/2 inhibition completely blocked migration induced by the combination CSF-1/PGE2. CSF-1/PGE2 functional interaction with respect to migration also occurre...Continue Reading

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Citations

Aug 9, 2008·International Immunopharmacology·Thomas G DouglassMartin R Jadus
Sep 3, 2016·Cell Adhesion & Migration·Graziana DigiacomoElisabetta Rovida
Aug 16, 2016·Blood Cells, Molecules & Diseases·Gulnaz T JavanShivani Soni
Jan 19, 2017·Journal of Clinical Medicine·Qiuchen GuoPepper Schedin
Dec 8, 2019·Cancer Immunology, Immunotherapy : CII·Paul L Crispen, Sergei Kusmartsev
Jan 25, 2017·Nature Reviews. Clinical Oncology·Alberto MantovaniPaola Allavena
Dec 15, 2019·International Journal of Molecular Sciences·Rei MizunoYoshiharu Sakai
May 21, 2020·Molecular Biology of the Cell·Emily F FoxTina L Tootle
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Hazel Y StevensKrishnendu Roy

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