title: Effects of IL8 and immune cells on the regulation of luteal progesterone secretion.
abstract: Recent studies have suggested that chemokines may mediate the luteolytic action of prostaglandin F2α (PGF). Our objective was to identify chemokines induced by PGF in vivo and to determine the effects of interleukin 8 (IL8) on specific luteal cell types in vitro. Mid-cycle cows were injected with saline or PGF, ovaries were removed after 0.5-4 h, and expression of chemokine was analyzed by qPCR. In vitro expression of IL8 was analyzed after PGF administration and with cell signaling inhibitors to determine the mechanism of PGF-induced chemokine expression. Purified neutrophils were analyzed for migration and activation in response to IL8 and PGF. Purified luteal cell types (steroidogenic, endothelial, and fibroblast cells) were used to identify which cells respond to chemokines. Neutrophils and peripheral blood mononuclear cells (PBMCs) were cocultured with steroidogenic cells to determine their effect on progesterone production. IL8, CXCL2, CCL2, and CCL8 transcripts were rapidly increased following PGF treatment in vivo. The stimulatory action of PGF on IL8 mRNA expression in vitro was prevented by inhibition of p38 and JNK signaling. IL8, but not PGF, TNF, or TGFB1, stimulated neutrophil migration. IL8 had no apparent action in purified luteal steroidogenic, endothelial, or fibroblast cells, but stimulated ERK phosphorylation in neutrophils. In coculture experiments neither IL8 nor activated neutrophils altered basal or LH-stimulated luteal cell progesterone synthesis. In contrast, activated PBMCs inhibited LH-stimulated progesterone synthesis from cultured luteal cells. These data implicate a complex cascade of events during luteolysis, involving chemokine signaling, neutrophil recruitment, and immune cell action within the corpus luteum.
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Talbott
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Abigail
authors.initials: A
authors.lastname: Delaney
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Yangsheng
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cushman
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Cupp
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5870, USADepartment of Obstetrics and GynecologyOlson Center for Women's Health, University of Nebraska Medical Center, Omaha, Nebraska 68198-3255, USADepartment of Pathology and MicrobiologyUniversity of Nebraska Medical Center, Omaha, Nebraska 68198-5900, USAUnited States Department of Agriculture-U.S. Meat Animal Research CenterClay Center, Nebraska 68933-0166, USADepartment of Animal ScienceUniversity of Nebraska-Lincoln, Lincoln, Nebraska 68583-0908, USAVA Nebraska Western Iowa Health Care System and Olson Center for Women's HealthDepartment of Obstetrics and Gynecology, University of Nebraska Medical Center, 983255 Nebraska Medical Center, Omaha, Nebraska 68198-3255, USA jsdavis@unmc.edu.
authors.forename: John S
authors.initials: JS
authors.lastname: Davis
mesh_terms: D000818:Animals; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D002633:Chemotaxis; D018920:Coculture Techniques; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D030762:Estrous Cycle; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D003341:Luteolysis / Q000187:drug effects; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D011374:Progesterone; D015237:Dinoprost