title: Dietary supplementation of soybean kunitz trypsin inhibitor reduces lipopolysaccharide-induced lethality in mouse model.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, 431-3192, Japan. hirokoba@hama-med.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Yoshida
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kanada
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yagyu
authors.forename: Kiyokazu
authors.initials: K
authors.lastname: Inagaki
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kondo
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurita
authors.forename: Mika
authors.initials: M
authors.lastname: Suzuki
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kanayama
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Terao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D007249:Inflammation; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D015398:Signal Transduction; D013025:Glycine max / Q000378:metabolism; D013997:Time Factors; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014360:Trypsin Inhibitor, Kunitz Soybean