{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T21:08:43Z","timestamp":1782335323837,"version":"3.54.5"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Secretory leukoprotease inhibitor (SLPI), an 11.7-kD nonglycosylated serine protease inhibitor, is produced and released into the fluids of mucosal surfaces including human lung. It comprises two domains with homologous amino acid sequences: the N-terminal domain possessing antibacterial activity, and the C-terminal domain with antiprotease activity. Here we report the positive regulation of hepatocyte growth factor (HGF) production in human lung fibroblasts exerted by SLPI or its C-terminal domain under physiologic concentrations (1 to 10 \u03bc M). This HGF production by SLPI was unaffected by the addition of interleukin (IL)-1 receptor antagonist. In contrast, human skin fibroblasts exerted no SLPI-stimulated increase in HGF production, despite the fact that IL-1 \u03b2 increased HGF production with an intensity similar to that of human lung fibroblasts. Both the time-course and dose-response studies in human lung fibroblasts revealed that the induction of HGF messenger RNA (mRNA) and protein occurred in parallel, indicating that the mechanism existed at the steady-state mRNA level. A synthetic elastase inhibitor failed to induce HGF, but \u03b11-antitrypsin also stimulated HGF production in lung fibroblasts. Inactivation of the antiprotease activity of SLPI or its C-terminal domain by an oxidizing agent (N-chlorosuccinimide) abolished their stimulatory effect on HGF production. These findings demonstrate that SLPI exerts a novel HGF induction and functions as an anti-inflammatory and regenerative factor in addition to its role in protease inhibition.<\/jats:p>","DOI":"10.1165\/ajrcmb.23.3.3942","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:47:41Z","timestamp":1365025661000},"page":"364-370","source":"Crossref","is-referenced-by-count":23,"title":["Secretory Leukoprotease Inhibitor Augments Hepatocyte Growth Factor Production in Human Lung Fibroblasts"],"prefix":"10.1093","volume":"23","author":[{"given":"Toshiaki","family":"Kikuchi","sequence":"first","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Yaekashiwa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mitsuhashi","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Satoh","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshikazu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Nukiwa","sequence":"additional","affiliation":[{"name":"Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, Sendai; Teijin Institute for Bio-Medical Research, Tokyo; and Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,9,1]]},"reference":[{"key":"2026030700050016300_B1"},{"key":"2026030700050016300_B2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/0167-4838(82)90095-4","article-title":"Kinetics of the inhibition of leukocyte elastase by the bronchial inhibitor.","volume":"700","author":"Gauthier","year":"1982","journal-title":"Biochim. 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Cytochem."},{"key":"2026030700050016300_B6","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S0092-8674(00)81880-2","article-title":"Secretory leukocyte protease inhibitor: a macrophage product induced by and antagonistic to bacterial lipopolysaccharide.","volume":"88","author":"Jin","year":"1997","journal-title":"Cell"},{"key":"2026030700050016300_B7","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1128\/IAI.66.6.2447-2452.1998","article-title":"Lipopolysaccharide-related stimuli induce expression of the secretory leukocyte protease inhibitor, a macrophage-derived lipopolysaccharide inhibitor.","volume":"66","author":"Jin","year":"1998","journal-title":"Infect. Immun."},{"key":"2026030700050016300_B8","doi-asserted-by":"crossref","first-page":"4520","DOI":"10.1128\/iai.64.11.4520-4524.1996","article-title":"Antibacterial activity of antileukoprotease.","volume":"64","author":"Hiemstra","year":"1996","journal-title":"Infect. Immun."},{"key":"2026030700050016300_B9","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1172\/JCI118056","article-title":"Secretory leukocyte protease inhibitor: a human saliva protein exhibiting anti-human immunodeficiency virus 1 activity in vitro.","volume":"96","author":"McNeely","year":"1995","journal-title":"J. Clin. 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Care Med."},{"key":"2026030700050016300_B14","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/oxfordjournals.jbchem.a021283","article-title":"Emerging multipotent aspects of hepatocyte growth factor.","volume":"119","author":"Matsumoto","year":"1996","journal-title":"J. Biochem."},{"key":"2026030700050016300_B15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1083\/jcb.127.1.225","article-title":"Regulation of scatter factor production via a soluble inducing factor.","volume":"127","author":"Rosen","year":"1994","journal-title":"J. Cell Biol."},{"key":"2026030700050016300_B16","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1006\/bbrc.1997.6358","article-title":"The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA.","volume":"232","author":"Zitnik","year":"1997","journal-title":"Biochem. Biophys. Res. 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