1. Dietary supplementation of soybean kunitz trypsin inhibitor reduces lipopolysaccharide-induced lethality in mouse model
- Author
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Yasufumi Kanada, Naohiro Kanayama, T. Yoichi Fukuda, Hiroshi Kobayashi, Toshihiko Terao, Toshiharu Kondo, Ryuji Yoshida, Mika Suzuki, Tatsuo Yagyu, Kiyokazu Inagaki, and Noriyuki Kurita
- Subjects
Lipopolysaccharides ,medicine.medical_specialty ,Time Factors ,Lipopolysaccharide ,MAP Kinase Signaling System ,medicine.medical_treatment ,p38 mitogen-activated protein kinases ,Trypsin inhibitor ,Blotting, Western ,Anti-Inflammatory Agents ,Administration, Oral ,Biology ,Critical Care and Intensive Care Medicine ,chemistry.chemical_compound ,Mice ,Intensive care ,Internal medicine ,medicine ,Animals ,Phosphorylation ,Inflammation ,Dose-Response Relationship, Drug ,Kinase ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Macrophages ,Trypsin ,Up-Regulation ,Enzyme Activation ,Mice, Inbred C57BL ,Dose–response relationship ,Cytokine ,Endocrinology ,chemistry ,Dietary Supplements ,Emergency Medicine ,Cytokines ,Female ,Soybeans ,Trypsin Inhibitor, Kunitz Soybean ,medicine.drug ,Interleukin-1 ,Signal Transduction - Abstract
We examined the modifying effects of a Kunitz trypsin inhibitor (KTI) and a Bowman-Birk trypsin inhibitor (BBI), purified from soybean, as intraperitoneal (i.p.) injection and dietary supplements on bacterial lipopolysaccharide (LPS)-induced lethality in mice. We initially examined the suppressing effects of i.p. injection of KTI (50 mg/kg) and BBI (50 mg/kg) on LPS-induced lethality after i.p. injection of LPS. Furthermore, groups of female C57BL/6 were fed a basal diet (control group) or the basal diet supplemented with KTI (50 g/kg) or BBI (50 g/kg). Here, we show that i.p. and daily oral administration of KTI, but not BBI, caused a significant reduction of the LPS-induced lethality; that LPS significantly induced plasma TNF-alpha, IL-1beta, and IL-6 levels in mice after LPS challenge; that concomitant administration of KTI, but not BBI, inhibits the LPS-induced plasma levels of these cytokines; and that KTI, but not BBI, suppressed LPS-induced upregulation of cytokine expression through suppression of phosphorylation of three mitogen-activated protein (MAP) kinase pathways, ERK1/2, JNK, and p38, in peritoneal macrophages. These data allow us to speculate that i.p. injection and dietary supplementation of a soybean KTI may play a role as a potent anti-inflammatory agent by inhibiting activation of MAP kinases, leading to the suppression of cytokine expression.
- Published
- 2005