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Citations to this article

Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester.
M Maruyama, … , C S Chu, R G Crystal
M Maruyama, … , C S Chu, R G Crystal
Published July 1, 1994
Citation Information: J Clin Invest. 1994;94(1):368-375. https://doi.org/10.1172/JCI117331.
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Modulation of secretory leukoprotease inhibitor gene expression in human bronchial epithelial cells by phorbol ester.

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Abstract

Secretory leukoprotease inhibitor (SLPI), a 12-kD nonglycosylated serine antiprotease, helps to protect the epithelial surface of the airways from the destructive capacity of neutrophil elastase. Based on the recognition that SLPI levels can increase in the presence of airway inflammation, we hypothesized that inflammatory stimuli should modulate the expression of the SLPI gene in airway epithelial cells. To evaluate this, the modulation of SLPI gene expression with various inflammatory stimuli was evaluated in the HS-24 human bronchial epithelial cell line. After preliminary studies showed that several inflammatory mediators enhanced SLPI messenger RNA (mRNA) levels, PMA was used as a model inflammatory stimulus. PMA significantly increased the level of 0.7-kb SLPI mRNA transcripts in HS-24 cells in a dose- and time-dependent fashion and increased the amount of SLPI protein in the culture supernatant. Nuclear run-on analyses showed that the SLPI gene transcription rate increased approximately twofold after PMA stimulation. Transfection studies using fusion genes composed of fragments of up to 1.2 kb of the 5' flanking sequence of the SLPI gene and a luciferase reporter gene demonstrated potent promoter activity in the 131-bp segment (-115 to +16 relative to the transcription start site), and all longer segments up to 1.2 kb, whereas smaller segments showed low promoter activity. An 18-bp element (-98 to -115), in a region with homology to PMA-responsive regions in the Moloney murine leukemia virus enhancer and the IL-8 gene, was shown to be of importance in the level of transcription of the SLPI gene. However, this element was not responsible for the upregulation of SLPI gene expression by PMA. Evaluation of HS-24 cells in the presence of actinomycin D demonstrated that SLPI mRNA transcripts were very stable and became more so in the presence of PMA. Thus, SLPI gene expression in airway epithelial cells can be upregulated by an inflammatory stimulus, and this modulation is regulated at both the transcriptional and posttranscriptional levels. These mechanisms of SLPI upregulation likely play a role in defending the epithelial surface in the local milieu of inflammatory lung diseases.

Authors

M Maruyama, J G Hay, K Yoshimura, C S Chu, R G Crystal

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Citations to this article (42)

Title and authors Publication Year
Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi-infected mice
Qian Y, Xiaotian T, Thomas H, Robert H, Belperron AA, Bockenstedt LK, Ring A, Nakamura A, Fikrig E
bioRxiv 2025
Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice.
Yu Q, Tang X, Hart T, Homer R, Belperron AA, Bockenstedt LK, Ring A, Nakamura A, Fikrig E
eLife 2025
The secretory leukocyte protease inhibitor (SLPI) in pathophysiology of non-communicable diseases: Evidence from experimental studies to clinical applications.
Mongkolpathumrat P, Pikwong F, Phutiyothin C, Srisopar O, Chouyratchakarn W, Unnajak S, Nernpermpisooth N, Kumphune S
Heliyon 2024
High expression of secretory leukocyte protease inhibitor (SLPI) in stage III micro-satellite stable colorectal cancer is associated with reduced disease recurrence.
Nugteren S, den Uil SH, Delis-van Diemen PM, Simons-Oosterhuis Y, Lindenbergh-Kortleve DJ, van Haaften DH, Stockmann HBAC, Sanders J, Meijer GA, Fijneman RJA, Samsom JN
Scientific Reports 2022
Endogenous secretory leukocyte protease inhibitor inhibits microbial-induced monocyte activation.
Nugteren S, Simons-Oosterhuis Y, Menckeberg CL, Hulleman-van Haaften DH, Lindenbergh-Kortleve DJ, Samsom JN
European Journal of Immunology 2022
Secretory Leukocyte Protease Inhibitor (SLPI) in mucosal tissues: protects against inflammation, but promotes cancer
S Nugteren, JN Samsom
Cytokine & Growth Factor Reviews 2021
Secretory leukocyte protease inhibitor and progranulin as possible regulators of cervical remodeling in pregnancy
T Samejima, T Nagamatsu, N Akiba, T Fujii, S Sayama, K Kawana, A Taguchi, K Kumasawa, T Iriyama, Y Osuga, T Fujii
Journal of Reproductive Immunology 2021
Identifying Biomarkers from Transcriptomic Signatures in Renal Allograft Biopsies Using Deceased and Living Donors
B Yang, N Sylvius, J Luo, C Yang, Z Da, C Crotty, ML Nicholson
Frontiers in immunology 2021
Expression of the immune modulator secretory leukocyte protease inhibitor (SLPI) in colorectal cancer liver metastases and matched primary tumors is associated with a poorer prognosis
S Nugteren, JA Goos, PM Diemen, Y Simons-Oosterhuis, DJ Lindenbergh-Kortleve, DH van Haaften, J Sanders, GA Meijer, RJ Fijneman, JN Samsom
OncoImmunology 2020
The Role of Secretory Leukocyte Proteinase Inhibitor During Transplantation
E Chuluyan, D Casadei, N Ambrosi, F Caro, D Guerrieri
Current Transplantation Reports 2019
Elevated concentration of secretory leukocyte protease inhibitor in the cervical mucus before delivery
T Samejima, T Nagamatsu, DJ Schust, N Itaoka, T Iriyama, T Nakayama, A Komatsu, K Kawana, Y Osuga, T Fujii
American Journal of Obstetrics and Gynecology 2016
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L Frew, SJ Stock
Reproduction 2011
Topley & Wilson's Microbiology and Microbial Infections
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Topley & Wilson's Microbiology and Microbial Infections 2010
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JM Sallenave
American journal of respiratory cell and molecular biology 2010
Serum and bronchial lavage fluid concentrations of IL-8, SLPI, sCD14 and sICAM-1 in patients with COPD and asthma
C Hollander, B Sitkauskiene, R Sakalauskas, U Westin, SM Janciauskiene
Respiratory Medicine 2007
Secretory leukocyte protease inhibitor and its potential interactions with elastase and cathepsin B in gingival crevicular fluid and saliva from patients with chronic periodontitis
SW Cox, EM Rodriguez-Gonzalez, V Booth, BM Eley
Journal of Periodontal Research 2006
Organization and promoter analysis of a tiger shrimp Penaeus monodon single WAP domain-containing protein gene
JY CHEN, JC CHEN, SH LIN, CY PAN, CM KUO
Fisheries Science 2006
Syk tyrosine kinase participates in β 1 -integrin signaling and inflammatory responses in airway epithelial cells
M Ulanova, L Puttagunta, M Marcet-Palacios, M Duszyk, U Steinhoff, F Duta, MK Kim, ZK Indik, AD Schreiber, AD Befus
American journal of physiology. Lung cellular and molecular physiology 2005
Human Immunodeficiency Virus Type 1 Stimulates the Expression and Production of Secretory Leukocyte Protease Inhibitor (SLPI) in Oral Epithelial Cells: a Role for SLPI in Innate Mucosal Immunity
NK Jana, LR Gray, DC Shugars
Journal of virology 2005
Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells
J Schlingemann, J Hess, G Wrobel, U Breitenbach, C Gebhardt, P Steinlein, H Kramer, G F�rstenberger, M Hahn, P Angel, P Lichter
International Journal of Cancer 2003
Increased expression of the secretory leukocyte proteinase inhibitor in Wegener's granulomatosis
S Ohlsson, R Falk, JJ Yang, K Ohlsson, M Segelmark, J Wieslander
Clinical & Experimental Immunology 2003
Novel distribution of the secretory leucocyte proteinase inhibitor in kidney
S Ohlsson, I Ljungkrantz, K Ohlsson, M Segelmark, J Wieslander
Mediators of Inflammation 2001
Cytokine-Mediated Induction of the Human Elafin Gene in Pulmonary Epithelial Cells Is Regulated by Nuclear Factor- κ B
L Bingle, TD Tetley, CD Bingle
American journal of respiratory cell and molecular biology 2001
Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands
H Saitoh, T Masuda, S Shimura, T Fushimi, K Shirato
American journal of physiology. Lung cellular and molecular physiology 2001
Constitutive and regulated secretion of secretory leukocyte proteinase inhibitor by human intestinal epithelial cells
M Si-Tahar, D Merlin, S Sitaraman, JL Madara
Gastroenterology 2000
Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins
S Wetering, AC van der Linden, MA van Sterkenburg, WI de Boer, AL Kuijpers, J Schalkwijk, PS Hiemstra
American journal of physiology. Lung cellular and molecular physiology 2000
Trout Ovulatory Proteins: Site of Synthesis, Regulation, and Possible Biological Function1
MA Coffman, JH Pinter, FW Goetz
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Reactive oxygen intermediates stimulate interleukin-6 production in human bronchial epithelial cells
Y Yoshida, M Maruyama, T Fujita, N Arai, R Hayashi, J Araya, S Matsui, N Yamashita, E Sugiyama, M Kobayashi
American journal of physiology. Lung cellular and molecular physiology 1999
Identification of the secretory leukocyte protease inhibitor (SLPI) as a target of IRF-1 regulation
H Nguyen, L Teskey, R Lin, J Hiscott
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Molecular Biology of the Lung
RA Stockley
1999
Induction of SLPI (ALP/HUSI-I) in Epidermal Keratinocytes
M Wingens, BH van Bergen, PS Hiemstra, JF Meis, IM van Vlijmen-Willems, PL Zeeuwen, J Mulder, HA Kramps, F Ruissen, J Schalkwijk
Journal of Investigative Dermatology 1998
Lipopolysaccharide-related stimuli induce expression of the secretory leukocyte protease inhibitor, a macrophage-derived lipopolysaccharide inhibitor
F Jin, CF Nathan, D Radzioch, A Ding
Infection and immunity 1998
Structure of the Murine Secretory Leukoprotease Inhibitor ( Slpi ) Gene and Chromosomal Localization of the Human and Murine SLPI Genes
T Kikuchi, T Abe, S Hoshi, N Matsubara, Y Tominaga, K Satoh, T Nukiwa
American journal of respiratory cell and molecular biology 1998
Molecular Basis of Sex Hormone Receptor Function
H Gronemeyer, U Fuhrmann, K Parczyk
1998
Secretory Leukocyte Protease Inhibitor: A Macrophage Product Induced by and Antagonistic to Bacterial Lipopolysaccharide
F Jin, C Nathan, D Radzioch, A Ding
Cell 1997
The elastase-induced expression of secretory leukocyte protease inhibitor is decreased in remodelled airway epithelium
V Marchand, JM Tournier, M Polette, B Nawrocki, C Fuchey, D Pierrot, H Burlet, E Puchelle
European Journal of Pharmacology 1997
Secretory leukocyte protease inhibitor (SLPI) in mucosal fluids inhibits HIV-1
SM Wahl, TB McNeely, EN Janoff, D Shugars, P Worley, C Tucker, JM Orenstein
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Bacterial Pneumonia Causes Augmented Expression of the Secretory Leukoprotease Inhibitor Gene in the Murine Lung
T Abe, Y Tominaga, T Kikuchi, A Watanabe, K Satoh, Y Watanabe, T Nukiwa
American journal of respiratory and critical care medicine 1997
The Cloning and Characterization of a Murine Secretory Leukocyte Protease Inhibitor cDNA
RJ Zitnik, J Zhang, MA Kashem, T Kohno, DE Lyons, CD Wright, E Rosen, I Goldberg, AC Hayday
Biochemical and Biophysical Research Communications 1997
Cis -acting Region Associated with Lung Cell-specific Expression of the Secretory Leukoprotease Inhibitor Gene
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