Interleukin-1beta upregulates functional expression of neurokinin-1 receptor (NK-1R) via NF-kappaB in astrocytes.
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.
Guo
Chang-Jiang
CJ
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.
Douglas
Steven D
SD
Gao
Zhiyong
Z
Wolf
Bryan A
BA
Grinspan
Judith
J
Lai
Jian-Ping
JP
Riedel
Eric
E
Ho
Wen-Zhe
WZ
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*
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