title: Professional phagocytic granulocyte-derived PGD2 regulates the resolution of inflammation in fish.
abstract: Prostaglandins (PGs) play a key role in the development on the immune response through the regulation of both pro- and anti-inflammatory processes. PGD(2) can be either pro- or anti-inflammatory depending on the inflammatory milieu. Prostaglandin D synthase (PGDS) is the enzyme responsible for the conversion of PGH(2) to PGD(2). In mammals, two types of PGDS synthase have been described, the hematopoietic (H-PGDS) and the lipocalin (L-PGDS). In the present study we describe the existence of two orthologs of the mammalian L-PGDS (PGDS1 and PGDS2) in the gilthead seabream and characterize their gene expression profiles and biological activity. The results showed a dramatic induction of the gene coding for PGDS1 in acidophilic granulocytes (AGs), which are functionally equivalent to mammalian neutrophils, after a prolonged in vitro activation with different pathogen associated molecular patterns (PAMPs). In contrast PGDS2 was not expressed in these cells. The functional relevance of the induction of PGDS1 in AGs was confirmed by the ability of these cells to release PGD(2) upon PAMP stimulation. To gain further insight into the role of PGD(2) in the resolution of inflammation in fish, we examined the ability of PGD(2) or its cyclopentenone derivates (cyPGs) to modulate the main functional activities of AGs. It was found that both PGD(2) and cyPGs inhibited the production of reactive oxygen species and downregulated the transcript levels of the gene encoding interleukin-1β. Taken together, these results demonstrate that the use of PGD(2) and its metabolites in the resolution of inflammation was established before the divergence of fish from tetrapods more than 450 million years ago and support a critical role for granulocytes in the resolution of inflammation in vertebrates.
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gómez-Abellán
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 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, 30100 Murcia, Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: López-Muñoz
authors.affiliation: Instituto de Investigaciones Marinas (IIM), Consejo Superior de Investigaciones Científicas (CSIC), Eduardo Cabello 6, 36208 Vigo, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Figueras
authors.affiliation: Oceanographic Centre of Murcia, Spanish Oceanographic Institute (IEO), Puerto de Mazarrón, 30860 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, 30100 Murcia, Spain.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Mulero
authors.affiliation: Department of Cell Biology and Histology, Faculty of Biology, University of Murcia, 30100 Murcia, Spain. Electronic address: mpsepul@um.es.
authors.forename: María P
authors.initials: MP
authors.lastname: Sepulcre
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005393:Fish Diseases / Q000276:immunology / Q000378:metabolism*; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D016905:Gram-Negative Bacterial Infections / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D006098:Granulocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000378:metabolism; D010587:Phagocytosis; D015230:Prostaglandin D2 / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D021541:Sea Bream / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D029941:Fish Proteins; D000069452:Pathogen-Associated Molecular Pattern Molecules; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2
keywords: Acidophilic granulocytes; Neutrophils; Prostaglandins; Seabream; Teleosts