title: Co-regulated decrease of Neurokinin-1 receptor and Hemokinin-1 gene expression in monocytes and macrophages after activation with pro-inflammatory cytokines.
abstract: Hemokinin-1 (HK-1), a potent ligand for the Neurokinin-1 receptor (NK-1) is thought to play a role in the immune system. To investigate the regulation of this receptor-ligand pair, we examined the effects of pro-inflammatory cytokines on their expression in the monocyte/macrophage cell lines Wehi-3 and RAW264.7. We demonstrate co-expression of NK-1 and HK-1 mRNA in both lines, as well as functional NK-1 receptor protein in Wehi-3 cells. Stimulation with IFN-gamma, IL-1beta and TNF-alpha markedly decreased NK-1 and HK-1 mRNA as well as NK-1 receptor protein, which coincided with monocytic differentiation. A co-regulated decrease could also be observed in differentiating primary bone marrow macrophages, suggesting that this receptor-ligand pair may be controlled by cytokine networks and may serve a developmental role in the immune system.
authors.affiliation: Princess Margaret Hospital, Ontario Cancer Institute, University Health Network, Department of Immunology, University of Toronto, 610 University Avenue, M5G 2M9 Toronto, Ontario, Canada. aberger@uhnres.utoronto.ca
authors.forename: Alexandra
authors.initials: A
authors.lastname: Berger
authors.forename: Anne H
authors.initials: AH
authors.lastname: Tran
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Paige
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009000:Monocytes / Q000187:drug effects*; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C507968:hemokinin-1; D002118:Calcium