New properties of the soybean trypsin inhibitor: Inhibition of human neutrophil elastase and its effect on acute pulmonary injury

Abstract

Seeds from legumes including the Gilcine max are known to be a rich source of protease inhibitors. The soybean Kunitz trypsin inhibitors (SKTIs) have been well characterised and have been found to exhibit many biological activities. However their effects on inflammatory diseases have not been studied to date. In this study, SKTI was purified using anion exchange chromatography using a Resource Q column. The purified protein was able to inhibit human neutrophil elastase (HNE) and bovine trypsin. Purified SKTI inhibited HNE with an IC(50) value of 8mug or 0.3nM. At this concentration SKTI showed neither cytotoxic nor haemolytic effects on human blood cell populations. SKTI showed no deleterious effects on organs, blood cells or the hepatic enzymes ALT and AST in the mouse model of acute systemic toxicity. Human neutrophils incubated with SKTI released less HNE than control neutrophils when stimulated with PAF or fMLP (83.1% and 70% respectively). These results showed that SKTI affected both pathways of elastase release by PAF and fMLP stimuli, suggesting that SKTI is an antagonist of fMLP/PAF receptors. In an in vivo mouse model of LPS acute lung injury, SKTI significantly suppressed the inflammatory effects caused by elastase in a dose-dependent manner. Histological sections stained by hematoxylin/eosin confirmed this decrease in inflammation. These results showed that SKTI could be used as a pharmacological agent for the therapy of many inflammatory diseases.

Lipotoxicity Causes Multisystem Organ Failure and Exacerbates Acute Pancreatitis in Obesity

“…Trypsin also increases the lipolytic response of adipocytes to adrenergic agents such as norepinephrine and isoproterenol (38). Addition of a serine protease–specific trypsin inhibitor (39) reduced the generation of glycerol when we cocultured adipocytes and acinar cells to 80% of that generated in its absence. This may partially explain how interstitial leakage of pancreatic enzymes affects lipolysis of adipocyte triglyceride.…”

The impacts of larval density and protease inhibition on feeding in medicinal larvae of the greenbottle fly Lucilia sericata

“…As its name suggests, SBTI is a strong inhibitor of trypsin and the Kunitz inhibitor used in this investigation also has a weak inhibitory effect on chymotrypsin (Ribeiro et al ., ). High‐activity SBTI is also a strong inhibitor of trypsin, but is reported to have no inhibitory effect on chymotrypsin (Uchino et al ., ).…”

Antimicrobial Activity of a Protease Inhibitor Isolated From the Rhizome of Curcuma Amada

“…These inhibitors have several biomedical and clinical applications, and the biological activities of these inhibitors in animal models have been reported [9][10][11]. C. amada has several medicinal values as claimed traditionally, and most of these values have been confirmed scientifically [6].…”