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 occurred in bone marrow-derived murine macrophages (EC₅₀ CSF-1, 6.7 ng/ml; EC₅₀ PGE2, 16.7 nM). These results indicated that PGE2 transactivates CSF-1R and synergizes with its signaling at ERK1/2 level in promoting macrophage migration.

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 / Digiacomo, Graziana; Ziche, Marina; Dello Sbarba, Persio; Donnini, Sandra; Rovida, Elisabetta. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - STAMPA. - 29:(2015), pp. 2545-2554. [10.1096/fj.14-258939]

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

DIGIACOMO, GRAZIANA;DELLO SBARBA, PERSIO;ROVIDA, ELISABETTA
2015

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 occurred in bone marrow-derived murine macrophages (EC₅₀ CSF-1, 6.7 ng/ml; EC₅₀ PGE2, 16.7 nM). These results indicated that PGE2 transactivates CSF-1R and synergizes with its signaling at ERK1/2 level in promoting macrophage migration.
2015
29
2545
2554
Digiacomo, Graziana; Ziche, Marina; Dello Sbarba, Persio; Donnini, Sandra; Rovida, Elisabetta
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1004993
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