title: Prostaglandin E2 promotes M2 polarization of macrophages via a cAMP/CREB signaling pathway and deactivates granulocytes in teleost fish.
abstract: The profile of prostaglandin (PG) production is determined by the differential expression of the enzymes involved in their production and degradation. Although the production of PGE2 by fish leukocytes has been relatively well studied in several fish species, knowledge of how its production is regulated, its biological activities and the signaling pathways activated by this PG is scant or even contradictory. In this work we show that in the teleost fish gilthead seabream (Sparus aurata L.) macrophages regulate PGE2 release mainly by inducing the expression of the genes encoding the enzymes responsible for its synthesis, while acidophilic granulocytes (AGs) not only induce these genes quickly after activation but also inhibit the expression of the genes encoding the enzymes responsible for PGE2 degradation at later time points. In addition, treatment of macrophages with PGE2 promoted their M2 polarization, which is characterized by high expression levels of interleukin-10, mannose-receptor c-type 1 and arginase 2 genes. In sharp contrast, PGE2 promoted the deactivation of AGs, since it decreased the production of reactive oxygen species and the expression of genes encoding pro-inflammatory cytokines. These differences are the result of the alternative signaling pathways used by PGE2 in macrophages and AGs, a cAMP/CREB signaling pathway operating in macrophages, but not in AGs, downstream of PGE2. Our data identify for the first time a role for professional phagocyte-derived-PGE2 in the resolution of inflammation in fish and highlight key differences in the PGE2 signaling pathway in macrophages and granulocytes.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain.
authors.forename: Jana
authors.initials: J
authors.lastname: Montero
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gómez-Abellán
authors.affiliation: Oceanographic Centre of Murcia, Spanish Oceanographic Institute (IEO), Puerto de Mazarrón, Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Arizcun
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain. Electronic address: vmulero@um.es.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, IMIB-Arrixaca, 30100 Murcia, Spain. Electronic address: mpsepul@um.es.
authors.forename: María P
authors.initials: MP
authors.lastname: Sepulcre
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000276:immunology*; D005393:Fish Diseases / Q000276:immunology* / Q000382:microbiology; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D008264:Macrophages / Q000276:immunology; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000276:immunology; D021541:Sea Bream; D014733:Vibrio / Q000502:physiology; D014735:Vibrio Infections / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*
chemical_list: D000069452:Pathogen-Associated Molecular Pattern Molecules; D015232:Dinoprostone
keywords: Acidophilic granulocytes; Evolution; Macrophages; Polarization; Prostaglandins; Teleosts