期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：5
页码：2957-2962
DOI：10.1073/pnas.0530112100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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-1{beta} increased the expression of the NK-1R gene at the mRNA and protein levels. Because IL-1{beta} function involves nuclear factor {kappa}B (NF-{kappa}B) activation, these data suggest that this increase in the expression of the NK-1R gene is mediated by the NF-{kappa}B transcription factor. An earlier report noted that the promoter region of the human NK-1R gene contains a putative binding site for NF-{kappa}B [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-{kappa}B-binding site, and that NF-{kappa}B 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-{kappa}B-dependent IL-1{beta} induction of the human NK-1R gene is regulated via a transcriptional event through this NF-{kappa}B 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-1{beta} or overexpression of NF-{kappa}B cDNAs resulted in a significant increase in the amount of luciferase activity that was diminished greatly in cells transfected with I{kappa}B, the NF-{kappa}B inhibitor. These results directly implicate NF-{kappa}B 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.
