Secretion of monocyte chemoattractant protein-1 by endothelial cells of the bovine corpus luteum: regulation by cytokines but not prostaglandin F2alpha.
Information regarding the regulation of monocyte chemoattractant protein-1 (MCP-1) in regression of the corpus luteum (CL) is limited. This study tested the hypothesis that endothelial cells derived from bovine CL are a source of MCP-1, and that proinflammatory cytokines, prostaglandin F2alpha (PGF2alpha), and progesterone regulate MCP-1 expression. Endothelial cells were treated without (Control) or with PGF2alpha (1 micro M), TNFalpha (100 ng/ml), interferon-gamma (IFNgamma, 200 IU/ml), and TNFalpha + IFNgamma for 24 and 48 h in the absence or presence of progesterone (P4, 250 ng/ml). Increases in MCP-1 mRNA and protein were observed in response to TNFalpha within 24 and 48 h of culture, respectively (P < 0.05). Interferon-gamma stimulated (P < 0.05) both MCP-1 mRNA and protein after 24 h of culture, and this effect was also sustained through 48 h of culture (P < 0.05). Cotreatment of cultures with TNFalpha + IFNgamma lead to further increases (P < 0.05) in MCP-1 in both 24- and 48-h cultures. Surprisingly, neither PGF2alpha nor P4 affected MCP-1 production. Subsequent experiments revealed that the endothelial cells lacked prostaglandin F2alpha receptor mRNA, and the MAPK pathway, although present and responsive to growth factor stimulation, was unresponsive to PGF2alpha stimulation. In summary, endothelial cells derived from bovine CL respond to TNFalpha and IFNgamma stimulation with an increase in MCP-1 secretion. In contrast, neither PGF2alpha nor P4 directly influenced endothelial expression of MCP-1. These results suggest that cytokines stimulate the synthesis of MCP-1 observed during PGF2alpha-induced luteal regression.
Department of Animal and Nutritional Sciences, University of New Hampshire-Durham, Durham, New Hampshire 03824, USA.
Victoria A
VA
Cavicchio
James K
JK
Pru
Benjamin S
BS
Davis
John S
JS
Davis
Bo R
BR
Rueda
David H
DH
Townson
D000818:Animals; D002232:Carbocyanines; D002417:Cattle; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003338:Corpus Luteum / Q000098:blood supply*; D016207:Cytokines / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011982:Receptors, Prostaglandin / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C035005:3,3'-dihexadecylindocarbocyanine; D002232:Carbocyanines; D018932:Chemokine CCL2; D016207:Cytokines; D005456:Fluorescent Dyes; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011982:Receptors, Prostaglandin; D014409:Tumor Necrosis Factor-alpha; C032629:acetyl-LDL; C034671:prostaglandin F2alpha receptor; D011374:Progesterone; D007371:Interferon-gamma; D015237:Dinoprost; D020928:Mitogen-Activated Protein Kinases