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Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2957-62. Epub 2003 Feb 19.

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

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Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.


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 alpha, 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.

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