title: Substance P downregulates expression of the high affinity IgE receptor (FcepsilonRI) by human mast cells.
abstract: The effect of the neuropeptide substance P (SP) on human mast cell (MC) phenotype is poorly understood. In this study, SP effects on human MC expression of the high affinity IgE receptor (FcepsilonRI) were characterized. SP downregulated expression of FcepsilonRI mRNA and protein by approximately 50% and in a concentration dependent manner, the effect was partially mediated by engagement of the neurokinin-1 receptor (NK1R) and resulted in reduced mast cell activation. Sensitization of MC with IgE prior to SP exposure protected MC from SP-mediated FcepsilonRI downregulation. SP release may inhibit MC responses to allergens and these results may have implications in neuroinflammatiion and stress.
authors.affiliation: Northwestern University Feinberg School of Medicine, Allergy-Immunology Division, 240 E Huron McGaw #M-327, Chicago, IL 60611, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: McCary
authors.forename: Brian P
authors.initials: BP
authors.lastname: Tancowny
authors.forename: Adriana
authors.initials: A
authors.lastname: Catalli
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Harris
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
authors.forename: Marianna
authors.initials: M
authors.lastname: Kulka
mesh_terms: D000485:Allergens / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017455:Receptors, IgE / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000485:Allergens; C543355:FcepsilonRI alpha-chain, human; D012333:RNA, Messenger; D017455:Receptors, IgE; D018040:Receptors, Neurokinin-1; D013373:Substance P; D007073:Immunoglobulin E