title: Prostaglandin E2 exerts the proapoptotic and antiproliferative effects on bovine NK cells.
abstract: The aim of this research was to determine whether prostaglandin E2 (PGE2) affects bovine NK cells in respect of their counts, apoptosis and proliferation, and if it does, then which of the PGE2 receptor (EP) subtype(s) mediate(s) these effects. We here report that long-term, but not short-term, exposure of bovine peripheral blood mononuclear cells to PGE2 at 10(-5)M, 10(-6)M and 10(-7)M, but not at 10(-8)M, caused a significant increase in the percentage of early apoptotic cells among NK cell subset. Moreover, PGE2 at 10(-5)M and 10(-6)M, but not at 10(-7)M and 10(-8)M, induced a considerable decrease in the absolute count of NK cells. The magnitude of these effects increased with an increasing concentration of PGE2. The blockade of EP1, EP2, EP3 and EP4 receptors did not prevent the PGE2-induced apoptosis and depletion of NK cells. The results suggest that the proapoptotic effect of PGE2 is secondary in character and the induction of this effect is not mediated through EP receptors. Furthermore, the studies demonstrated that PGE2 at 10(-5)M and 10(-6)M, but not at 10(-7)M and 10(-8)M, highly significantly reduced the percentage of proliferating NK cells. The EP1, EP1/2 and EP3 receptor antagonists were unable to block this effect significantly, whereas the selective blockade of EP4 receptors prevented the PGE2-induced inhibition of NK cells proliferation. These results indicate that PGE2 at certain concentrations may impair the proliferation of NK cells and this effect is mediated via the EP4 receptor.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland. Electronic address: tomasz.maslanka@uwm.edu.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Maślanka
authors.affiliation: Wipasz S.A., Wadąg 9, 10-373 Olsztyn, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Chrostowska
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Otrocka-Domagała
authors.affiliation: Department of Internal Medicine, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 14, 10-719 Olsztyn, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Snarska
authors.affiliation: Department of Internal Medicine, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 14, 10-719 Olsztyn, Poland.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Mikiewicz
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Zuśka-Prot
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jasiecka
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
authors.forename: Hubert
authors.initials: H
authors.lastname: Ziółkowski
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Markiewicz
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Oczapowskiego Street 13, 10-719 Olsztyn, Poland.
authors.forename: Jerzy J
authors.initials: JJ
authors.lastname: Jaroszewski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle / Q000097:blood*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D007694:Killer Cells, Natural / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism
chemical_list: D018078:Receptors, Prostaglandin E; D015232:Dinoprostone
keywords: Apoptosis; Cattle; EP receptor; NK cells; PGE(2); Proliferation