title: Interleukin-1beta upregulates functional expression of neurokinin-1 receptor (NK-1R) via NF-kappaB in astrocytes.
abstract: Cytokines and neuropeptides are modulators of neuroimmunoregulation in the central nervous system (CNS). The interaction of these modulators may have important implications in CNS diseases. We investigated whether interleukin-1beta (IL-1beta) modulates the expression of neurokinin-1 receptor (NK-1R), the primary receptor for substance P (SP), a potent neuropeptide in the CNS. IL-1beta upregulated NK-1R expression in human astroglioma cells (U87 MG) and primary rat astrocytes at both mRNA and protein levels. IL-1beta treatment of U87 MG cells and primary rat astrocytes led to an increase in cytosolic Ca(2+) in response to SP stimulation, indicating that IL-1beta-induced NK-1R is functional. CP-96,345, a specific non-peptide NK-1R antagonist, inhibited SP-induced rise of [Ca(2+)](i) in the astroglioma cells. Investigation of the mechanism responsible for IL-1beta action revealed that IL-1beta has the ability of activating nuclear factor-kappab (NF-kappaB). Caffeic acid phenethyl ester (CAPE), a specific inhibitor of NF-kappaB activation, not only abrogated IL-1beta-induced NF-kappaB promoter activation, but also blocked IL-1beta-mediated induction of NK-1R gene expression. These findings provide additional evidence that there is a biological interaction between IL-1beta and the neuropeptide SP in the CNS, which may have important implications in the inflammatory diseases in the CNS.
authors.affiliation: Division of Allergy and Immunology, Department of Pediatrics, Joseph Stokes Jr. Research Institute of Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Chang-Jiang
authors.initials: CJ
authors.lastname: Guo
authors.forename: Steven D
authors.initials: SD
authors.lastname: Douglas
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Gao
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Wolf
authors.forename: Judith
authors.initials: J
authors.lastname: Grinspan
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Lai
authors.forename: Eric
authors.initials: E
authors.lastname: Riedel
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004660:Encephalitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D016328:NF-kappa B / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*
chemical_list: D001713:Biphenyl Compounds; D002109:Caffeic Acids; D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D013373:Substance P; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D002118:Calcium; C066892:CP 96345