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Regulation of the NK-1 receptor gene expression in human macrophage cells via an NF-κB site on its promoter

By Simos Simeonidis, Ignazio Castagliuolo, Amy Pan, Jennifer Liu, Chi-Chi Wang, Andreas Mykoniatis, Asia Pasha, Leyla Valenick, Stavros Sougioultzis, Dezheng Zhao and Charalabos Pothoulakis

Abstract

We report here that human monocytic/macrophage THP-1 cells express the neurokinin 1 receptor (NK-1R), and that exposure of these cells to the proinflammatory cytokine IL-1β increased the expression of the NK-1R gene at the mRNA and protein levels. Because IL-1β function involves nuclear factor κB (NF-κB) activation, these data suggest that this increase in the expression of the NK-1R gene is mediated by the NF-κB transcription factor. An earlier report noted that the promoter region of the human NK-1R gene contains a putative binding site for NF-κB [Takahashi, K., Tanaka, A., Hara, M. & Nakanishi, S. (1992) Eur. J. Biochem. 204, 1025–1033]. Here we demonstrate that this is indeed a functional NF-κB-binding site, and that NF-κB is responsible for regulating the expression of the NK-1R gene by binding to the promoter region of the NK-1R gene. To further substantiate that the observed NF-κB-dependent IL-1β induction of the human NK-1R gene is regulated via a transcriptional event through this NF-κB site on the NK-1R gene promoter, we transfected THP-1 cells with a luciferase promoter-reporter construct containing the 5′ promoter region of the human NK-1R gene. Exposure of these cells to IL-1β or overexpression of NF-κB cDNAs resulted in a significant increase in the amount of luciferase activity that was diminished greatly in cells transfected with IκBα, the NF-κB inhibitor. These results directly implicate NF-κB in the regulation of the NK-1R gene and provide a molecular mechanism for the increase in expression of the NK-1R gene in responsive cells

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2003
DOI identifier: 10.1073/pnas.0530112100
OAI identifier: oai:pubmedcentral.nih.gov:151448
Provided by: PubMed Central
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