scholarly journals Secretory leukocyte protease inhibitor promising protective roles in obesity-associated atherosclerosis

2016 ◽  
Vol 242 (3) ◽  
pp. 250-257 ◽  
Author(s):  
Qiao-Qing Zhong ◽  
Xiang Wang ◽  
Yun-Feng Li ◽  
Li-Jun Peng ◽  
Zhi-Sheng Jiang
Keyword(s):  
Protease Inhibitor ◽  
Inflammatory Responses ◽  
Plaque Rupture ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Metabolic Dysfunction ◽  
Arterial Plaque ◽  
Atherosclerosis Development ◽  
Anti Fungal

Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor, which was most commonly examined in mucosal fluids such as saliva, is a versatile molecule and plays non-redundant roles. In addition to its anti-protease activity, SLPI has been shown to express anti-bacterial, anti-viral, anti-fungal, and anti-inflammatory properties as well as participating in innate and adaptive immune responses, most of which has been well documented. Recently, it is reported that SLPI is expressed in adipocytes and adipose tissue where it could play an important feedback role in the resolution of inflammation. Furthermore, circulating SLPI has been shown to correlate with progressive metabolic dysfunction. Moreover, adenoviral gene delivery of elafin and SLPI attenuates nuclear factor-κB-dependent inflammatory responses of human endothelial cells and macrophages to atherogenic stimuli. This review contributes to unraveling the protective role of SLPI in obesity-related atherosclerosis development, and the potential role in preventing arterial plaque rupture.

scholarly journals Secretory leukocyte protease inhibitor concentration increases in amniotic fluid with the onset of labour in women: characterization of sites of release within the uterus

1999 ◽  
Vol 161 (2) ◽  
pp. 299-306 ◽  
Author(s):  
FC Denison ◽  
RW Kelly ◽  
AA Calder ◽  
SC Riley
Keyword(s):  
Protease Inhibitor ◽  
Amniotic Fluid ◽  
Inflammatory Responses ◽  
Elective Caesarean Section ◽  
Fetal Lung ◽  
Neutrophil Function ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Decidua Basalis ◽  
Chorion Laeve

Secretory leukocyte protease inhibitor is a potent inhibitor of neutrophil function, a mediator of mucosal immunity and an inhibitor of NF|gkB regulated inflammatory responses. However, its source, function and regulation within the uterus during pregnancy and at parturition are not well defined. In amniotic fluid, the concentration of secretory leukocyte protease inhibitor increased significantly from 2nd trimester (24+/-3 ng/ml; mean+/-s.e.m.; n=20) to term (751+/-53 ng/ml; P<0.05; n=15) with a further profound increase (P<0.005) with the onset of labour (3929+/-1076 ng/ml; n=15). To establish the intra-uterine sites of secretion, explants (n=6 different patients per tissue) were collected at term after elective caesarean section. High levels of secretory leukocyte protease inhibitor were released by decidua (135.2+/-12.4 pg/mg; mean+/-s.e.m.) and chorio-decidua (325.1+/-26.4 pg/mg) with less by amnion (55.6+/-6.0 pg/mg) and placenta (9.2+/-1.9 pg/mg). Intense immunoreactivity for secretory leukocyte protease inhibitor was detected predominantly in decidua parietalis cells adherent to the chorion laeve and myometrium, and also in decidua basalis. We propose that, within the pregnant uterus, secretory leukocyte protease inhibitor is released by decidua, fetal membranes and potentially the fetal lung. The increase in secretory leukocyte protease inhibitor may act to modulate pro-inflammatory paracrine interactions for the maintenance of pregnancy and limit those occurring at parturition within the uterus.

The alarm secretory leukocyte protease inhibitor increases with progressive metabolic dysfunction

2011 ◽  
Vol 412 (11-12) ◽  
pp. 1122-1126 ◽  
Author(s):  
Abel López-Bermejo ◽  
Francisco J. Ortega ◽  
Antoni Castro ◽  
Wifredo Ricart ◽  
José-Manuel Fernández-Real
Keyword(s):  
Protease Inhibitor ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Metabolic Dysfunction

scholarly journals Secretory leukocyte protease inhibitor: A pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure

Hepatology ◽  
2014 ◽  
Vol 59 (4) ◽  
pp. 1564-1576 ◽  
Author(s):  
Charalambos Gustav Antoniades ◽  
Wafa Khamri ◽  
Robin D. Abeles ◽  
Leonie S. Taams ◽  
Evangelos Triantafyllou ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Inflammatory Responses ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Anti Inflammatory

scholarly journals AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury

2019 ◽  
Vol 316 (3) ◽  
pp. G387-G396 ◽  
Author(s):  
Zhen-Tang Jing ◽  
Wei Liu ◽  
Chao-Rong Xue ◽  
Shu-Xiang Wu ◽  
Wan-Nan Chen ◽  
...  
Keyword(s):  
Liver Injury ◽  
Inflammatory Responses ◽  
Metabolic Activation ◽  
Nuclear Factor Κb ◽  
Protective Role ◽  
Hepatocyte Apoptosis ◽  
Akt Inhibitor ◽  
Inhibitory Protein ◽  
Tnf Α ◽  
Induced Apoptosis

Tumor necrosis factor-α (TNF-α) is a highly pleiotropic cytokine executing biological functions as diverse as cell proliferation, metabolic activation, inflammatory responses, and cell death. TNF-α can induce multiple mechanisms to initiate apoptosis in hepatocytes leading to the subsequent liver injury. Since the phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) pathway is known to have a protective role in death factor-mediated apoptosis, it is our hypothesis that activation of Akt may represent a therapeutic strategy to alleviate TNF-α-induced hepatocyte apoptosis and liver injury. We report here that the Akt activator SC79 protects hepatocytes from TNF-α-induced apoptosis and protects mice from d-galactosamine (d-Gal)/lipopolysaccharide (LPS)-induced TNF-α-mediated liver injury and damage. SC79 not only enhances the nuclear factor-κB (NF-κB) prosurvival signaling in response to TNF-α stimulation, but also increases the expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein L and S (FLIPL/S), which consequently inhibits the activation of procaspase-8. Furthermore, pretreatment of the PI3K/Akt inhibitor LY294002 reverses all the SC79-induced hepatoprotective effects. These results strongly indicate that SC79 protects against TNF-α-induced hepatocyte apoptosis and suggests that SC79 is likely a promising therapeutic agent for ameliorating the development of liver injury. NEW & NOTEWORTHY SC79 protects hepatocytes from TNF-α-mediated apoptosis and mice from Gal/LPS-induced liver injury and damage. Cytoprotective effects of SC79 against TNF-α act through both AKT-mediated activation of NF-κB and upregulation of FLIPL/S.

Potential protective role of secretory leukocyte protease inhibitor (SLPI) in transplanted organs

Pneumologie ◽  
2016 ◽  
Vol 70 (07) ◽  
Author(s):  
A Zakrzewicz ◽  
S Wilker ◽  
S Stumpf ◽  
K Petrie ◽  
W Padberg ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Protective Role ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Transplanted Organs

scholarly journals Lipopolysaccharide-Related Stimuli Induce Expression of the Secretory Leukocyte Protease Inhibitor, a Macrophage-Derived Lipopolysaccharide Inhibitor

1998 ◽  
Vol 66 (6) ◽  
pp. 2447-2452 ◽  
Author(s):  
Fenyu Jin ◽  
Carl F. Nathan ◽  
Danuta Radzioch ◽  
Aihao Ding
Keyword(s):  
Protease Inhibitor ◽  
Inflammatory Responses ◽  
Interleukin 10 ◽  
Secretory Leukocyte Protease Inhibitor ◽  
No Production ◽  
Gram Positive ◽  
Gram Negative ◽  
Anti Inflammatory

ABSTRACT Mouse secretory leukocyte protease inhibitor (SLPI) was recently characterized as a lipopolysaccharide (LPS)-induced product of macrophages that antagonizes their LPS-induced activation of NF-κB and production of NO and tumor necrosis factor (TNF) (F. Y. Jin, C. Nathan, D. Radzioch, and A. Ding, Cell 88:417–426, 1997). To better understand the role of SLPI in innate immune and inflammatory responses, we examined the kinetics of SLPI expression in response to LPS, LPS-induced cytokines, and LPS-mimetic compounds. SLPI mRNA was detectable in macrophages by Northern blot analysis within 30 min of exposure to LPS but levels peaked only at 24 to 36 h and remained elevated at 72 h. Despite the slowly mounting and prolonged response, early expression of SLPI mRNA was cycloheximide resistant. Two LPS-induced proteins—interleukin-10 (IL-10) and IL-6—also induced SLPI, while TNF and IL-1β did not. The slow attainment of maximal induction of SLPI by LPS in vitro was mimicked by infection with Pseudomonas aeruginosa in vivo, where SLPI expression in the lung peaked at 3 days. Two LPS-mimetic molecules—taxol from yew bark and lipoteichoic acid (LTA) from gram-positive bacterial cell walls—also induced SLPI. Transfection of macrophages with SLPI inhibited their LTA-induced NO production. An anti-inflammatory role for macrophage-derived SLPI seems likely based on SLPI’s slowly mounting production in response to constituents of gram-negative and gram-positive bacteria, its induction both as a direct response to LPS and as a response to anti-inflammatory cytokines induced by LPS, and its ability to suppress the production of proinflammatory products by macrophages stimulated with constituents of both gram-positive and gram-negative bacteria.

Oxidative Stress and Atherosclerosis: Its Relationship to Growth Factors, Thrombus Formation and Therapeutic Approaches

1999 ◽  
Vol 82 (S 01) ◽  
pp. 32-37 ◽  
Author(s):  
Karlheinz Peter ◽  
Wolfgang Kübler ◽  
Johannes Ruef ◽  
Thomas K. Nordt ◽  
Marschall S. Runge ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factors ◽  
Vessel Wall ◽  
Inflammatory Responses ◽  
Plaque Rupture ◽  
Thrombus Formation ◽  
Vascular Lesion ◽  
Coagulation System ◽  
Therapeutic Approaches ◽  
Causative Relationship

SummaryThe initiating event of atherogenesis is thought to be an injury to the vessel wall resulting in endothelial dysfunction. This is followed by key features of atherosclerotic plaque formation such as inflammatory responses, cell proliferation and remodeling of the vasculature, finally leading to vascular lesion formation, plaque rupture, thrombosis and tissue infarction. A causative relationship exists between these events and oxidative stress in the vessel wall. Besides leukocytes, vascular cells are a potent source of oxygen-derived free radicals. Oxidants exert mitogenic effects that are partially mediated through generation of growth factors. Mitogens, on the other hand, are potent stimulators of oxidant generation, indicating a putative self-perpetuating mechanism of atherogenesis. Oxidants influence the balance of the coagulation system towards platelet aggregation and thrombus formation. Therapeutic approaches by means of antioxidants are promising in both experimental and clinical designs. However, additional clinical trials are necessary to assess the role of antioxidants in cardiovascular disease.

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