T Kikuchi, T Abe, K Satoh, K Narumi, T Sakai, S Abe, S Shindoh, K Matsushima and T Nukiwa
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. kikuchi@idac.tohoku.ac.jp

Secretory leukoprotease inhibitor (SLPI) is a serine protease inhibitor, produced locally in respiratory and genital glands, but not in the liver. In the present study the promoter region of this gene was analyzed to better understand the molecular mechanisms involved in transcriptional regulation. DNase-I hypersensitive sites were detected within 1 kbp upstream of exon I in chromatin structures of type II pneumocyte cell line A549 and utero-cervical cell line HeLa, both of which express SLPI mRNA transcripts. The function of the SLPI promoter encompassing these DNase-I hypersensitive sites has been studied by deletion analysis with the luciferase gene as a transient expression vector. In this analysis, we found three transcription control regions that function in A549 cells but not in nonlung cell lines, such as HeLa and hepatoma Hep G2. Among three cis-regulatory regions, a proximal 41- bp region (-132 to -92 bp relative to the transcription start site) is responsible for the most striking magnitude of transcriptional activity. This region corresponds to the transcriptional activating sequence detected in another lung cell line, HS-24, indicating that this 41-bp sequence is required for lung cell-specific expression. An electrophoretic mobility shift assay demonstrated that this 41-bp promoter region contains an 11-bp recognition sequence for two nuclear binding proteins, one of which is abundant in lung cell lines, and the other in nonlung cell lines. These results suggest that the ratio of these two nuclear binding proteins confers the cell type specificity on the expression pattern of the SLPI gene.

This article has been cited by other articles:

				M. Maemondo, Y. Saijo, K. Narumi, T. Kikuchi, K. Usui, R. Tazawa, K. Matsumoto, T. Nakamura, K. Sasaki, M. Takahashi, et al. Gene Therapy with Secretory Leukoprotease Inhibitor Promoter-Controlled Replication-Competent Adenovirus for Non-Small Cell Lung Cancer Cancer Res., July 1, 2004; 64(13): 4611 - 4620. [Abstract] [Full Text] [PDF]

				K. Hagiwara, T. Kikuchi, Y. Endo, Huqun, K. Usui, M. Takahashi, N. Shibata, T. Kusakabe, H. Xin, S. Hoshi, et al. Mouse SWAM1 and SWAM2 Are Antibacterial Proteins Composed of a Single Whey Acidic Protein Motif J. Immunol., February 15, 2003; 170(4): 1973 - 1979. [Abstract] [Full Text] [PDF]

				L. Bingle, T. D. Tetley, and C. D. Bingle Cytokine-Mediated Induction of the Human Elafin Gene in Pulmonary Epithelial Cells Is Regulated by Nuclear Factor-kappa B Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 84 - 91. [Abstract] [Full Text] [PDF]

				H. Saitoh, T. Masuda, S. Shimura, T. Fushimi, and K. Shirato Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L79 - L87. [Abstract] [Full Text] [PDF]

				T. Kikuchi, T. Abe, S. Hoshi, N. Matsubara, Y. Tominaga, K. Satoh, and T. Nukiwa Structure of the Murine Secretory Leukoprotease Inhibitor (Slpi) Gene and Chromosomal Localization of the Human and Murine SLPI Genes Am. J. Respir. Cell Mol. Biol., December 1, 1998; 19(6): 875 - 880. [Abstract] [Full Text]