Regulation of the NK-1 receptor gene expression in human macrophage cells via an NF-kappa B site on its promoter.
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.[1]References
- Regulation of the NK-1 receptor gene expression in human macrophage cells via an NF-kappa B site on its promoter. Simeonidis, S., Castagliuolo, I., Pan, A., Liu, J., Wang, C.C., Mykoniatis, A., Pasha, A., Valenick, L., Sougioultzis, S., Zhao, D., Pothoulakis, C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
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