Transforming growth factor-β1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line

Jaumann, F.; Elssner, Andreas; Mazur, G; Dobmann, Sandra; Vogelmeier, Claus; Group, for the Munich Lung Transplant

doi:10.1034/j.1399-3003.2000.01513.x

Cited by 34 publications

(30 citation statements)

References 36 publications

(29 reference statements)

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“…For LOX, this is a likely possibility because it is a known transcriptional target of TGF-␤1 (65). The intermediate steps leading to the inhibition of TGF-␤1 and IGFBP-3 gene expression upon increased expression of SLPI cannot be deduced from the present studies, although a regulatory loop arising from TGF-␤1 inhibition of SLPI gene expression, as demonstrated here, is consistent with reports observed for a bronchial epithelial cell line (66). In further agreement with the present results, a negative correlation between SLPI and TGF-␤1 was reported in SLPI null mutant mice (25).…”

Section: Fig 8 Effects Of Tgf-␤1 On Ishikawa Cell Gene Expressionsupporting

confidence: 91%

Secretory Leukocyte Protease Inhibitor Mediates Proliferation of Human Endometrial Epithelial Cells by Positive and Negative Regulation of Growth-associated Genes

Zhang

Simmen

Michel

et al. 2002

Journal of Biological Chemistry

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Secretory leukocyte protease inhibitor (SLPI) inhibits chymotrypsin, trypsin, elastase, and cathepsin G. This protein also exhibits proliferative effects, although little is known about the molecular mechanisms underlying this activity. We have generated SLPI-ablated epithelial sublines by stably transfecting the Ishikawa human endometrial cell line with an antisense human SLPI RNA expression vector. We demonstrate a positive correlation between cellular SLPI production and proliferation. We further show that Ishikawa sublines expressing low to undetectable SLPI have correspondingly increased and decreased expression, respectively, of transforming growth factor-␤1 and cyclin D1 genes, relative to parental cells. SLPI selectively increased cyclin D1 gene expression, with the effect occurring in part at the level of promoter activity. Cellular SLPI levels negatively influenced the anti-proliferative and pro-apoptotic insulin-like growth factor-binding protein-3 expression. We also identified lysyl oxidase, a phenotypic inhibitor of the ras oncogenic pathway and a tumor suppressor, as SLPI-repressed gene, whose expression is up-regulated by transforming growth factor-␤1. Our results suggest that SLPI acts at the node(s) of at least three major interacting growth inhibitory pathways. Because expression of SLPI is generally high in epithelial cells exhibiting abnormal proliferation such as in carcinomas, SLPI may define a novel pathway by which cellular growth is modulated. Secretory leukocyte protease inhibitor (SLPI),1 also known as anti-leukoprotease, human mucus proteinase inhibitor, and human seminal plasma inhibitor, is a 12-kDa member of the chelonianin class of serine protease inhibitors, which also includes SKALP/elafin (1, 2). SLPI is composed of two homologous cysteine-rich domains. The carboxyl-terminal domain manifests inhibitory activities against chymotrypsin, trypsin, granulocyte and pancreatic elastases, cathepsin G, and mast cell chymase (3, 4). SLPI is expressed primarily in secretory/glandular epithelial cells of a variety of human tissues including the bronchi, parotid glands, small and large intestines, skin, breast, pancreas, male and female genital tracts, and kidney (5-14). Its relative absence in serum, except in certain pathological conditions (15, 16), and its localization to extracellular matrix and subcellular sites not readily accessible to larger molecular weight protease inhibitors such as ␣ 1 -antitrypsin (17), suggests a primarily autocrine/paracrine mode of action. In addition to its anti-protease activity, SLPI has anti-inflammatory, anti-bacterial, anti-fungal, and anti-retroviral (human immunodeficiency virus) activities that appear to reside in its amino-terminal cysteine-rich domain (18 -23). Furthermore, SLPI has been shown to regulate intracellular enzyme synthesis, suppress matrix metalloproteinase production and activity, mediate normal wound healing, prevent scar formation, and augment fertility (24 -27). The higher uterine endometrial expression of SLPI during pregnancy ...

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Section: Fig 8 Effects Of Tgf-␤1 On Ishikawa Cell Gene Expressionsupporting

confidence: 91%

Secretory Leukocyte Protease Inhibitor Mediates Proliferation of Human Endometrial Epithelial Cells by Positive and Negative Regulation of Growth-associated Genes

Zhang

Simmen

Michel

et al. 2002

Journal of Biological Chemistry

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“…Oral and genital mucosae differ in several aspects that may alter their susceptibility to this virus, including the architecture of the epithelium, composition and viscosity of the fluids bathing the sites, and local immune responses. In addition, tissue-specific differences in SLPI regulation by HIV-1 may contribute to tissue susceptibility, as treatment with tumor growth factor ␤1 suppressed SLPI mRNA levels in respiratory epithelial cells (21) but had the opposite effect in endometrial epithelial cells (50). Characterization of the SLPI response to HIV-1 in nonoral mucosal tissues will shed light on this important issue.…”

Section: Discussionmentioning

confidence: 99%

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

Jana¹,

Gray

Shugars

2005

J Virol

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The innate immune response is a key barrier against pathogenic microorganisms such as human immunodeficiency virus type 1 (HIV-1). Because HIV-1 is rarely transmitted orally, we hypothesized that oral epithelial cells participate in the innate immune defense against this virus. We further hypothesized that secretory leukocyte protease inhibitor (SLPI), a 12-kDa mucosal antiviral protein, is a component of the host immune response to this virus. Here we demonstrated constitutive expression and production of SLPI in immortalized human oral keratinocytes. Brief exposure of cells to HIV-1 BaL and HXB2 significantly increased SLPI mRNA and protein production compared to that in mock-exposed cells (P < 0.01), as evaluated by real-time quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. HIV-1-mediated stimulation of SLPI occurred at the transcriptional level, was dose and time dependent, was elicited by heat-inactivated and infectious viruses, and did not depend on cellular infection. Experiments with purified retroviral proteins showed that the stimulatory effect was induced specifically by external envelope glycoproteins from HIV-1 and simian immunodeficiency virus. SLPI responsiveness to HIV-1 was also observed in an unrelated oral epithelial cell line and in normal (nonimmortalized) human oral epithelial cells isolated from healthy uninfected gingival tissues. In this first report of SLPI regulation by HIV-1, we show that the expression and production of the antimicrobial and anti-inflammatory protein can be stimulated in oral epithelial cells by the virus through interactions with gp120 in the absence of direct infection. These findings indicate that SLPI is a component of the oral mucosal response to HIV-1.

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“…strated in cultured keratinocytes (Tanaka et al, 2000); or in turn, SLPI might suppress inflammatory cytokine gene expression as shown after hepatic ischemic reperfusion injury (Lentsch et al, 1999) or affect cytokine activity (such as TGF-␤) as shown in cutaneous wound healing in SLPI-null mice (Ashcroft et al, 2000). In addition, the expression of SLPI preceded that of TGF-␤1 after ischemic brain injury (Wang et al, 1995), and TGF-␤1 was shown to inhibit SLPI expression in cultured bronchial epithelial cells (Jaumann et al, 2000). The temporal expression profile of SLPI with inflammatory mediators and leukocyte accumulation in the brain after ischemic injury again suggests that SLPI may be associated with regulation of inflammatory response.…”

Section: Slpi Expression Protects Brain From Ischemic Injury 837mentioning

confidence: 99%

Up-Regulation of Secretory Leukocyte Protease Inhibitor (SLPI) in the Brain after Ischemic Stroke: Adenoviral Expression of SLPI Protects Brain from Ischemic Injury

Wang

Li²,

Xu³

et al. 2003

Mol Pharmacol

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Secretory leukocyte protease inhibitor (SLPI) is a 12-kDa secreted protein initially identified from epithelial cells as an inhibitor of leukocyte serine proteases. In the present study, we described the identification of SLPI expression in ischemic cortex by suppression subtractive hybridization strategy. Our full-length rat SLPI cDNA shares 81% and 63% amino acid sequence identity with its mouse and human homologs, respectively, and with several polymorphisms to previous reported rat sequences. Northern blot analysis confirmed that SLPI mRNA was significantly induced in the ischemic brain tissue at 12 h (5

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Transforming growth factor-β1 is a potent inhibitor of secretory leukoprotease inhibitor expression in a bronchial epithelial cell line

Cited by 34 publications

References 36 publications

Secretory Leukocyte Protease Inhibitor Mediates Proliferation of Human Endometrial Epithelial Cells by Positive and Negative Regulation of Growth-associated Genes

Secretory Leukocyte Protease Inhibitor Mediates Proliferation of Human Endometrial Epithelial Cells by Positive and Negative Regulation of Growth-associated Genes

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

Up-Regulation of Secretory Leukocyte Protease Inhibitor (SLPI) in the Brain after Ischemic Stroke: Adenoviral Expression of SLPI Protects Brain from Ischemic Injury

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