Nov 24, 2005

Suppression of lipopolysaccharide-induced cytokine production of gingival fibroblasts by a soybean, Kunitz trypsin inhibitor

Journal of Periodontal Research
Hiroshi KobayashiToshihiko Terao

Abstract

Human bikunin, a Kunitz-type trypsin inhibitor, inhibits inflammation by down-regulating the expression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) in tumor cells and inflammatory cells. We analyzed the effect of a soybean-derived Kunitz trypsin inhibitor (KTI) on TNF-alpha production in human gingival fibroblasts stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Mitogen-activated protein kinase (MAPK) activation and cytokine levels were monitored using western blot and a specific enzyme-linked immunosorbent assay (ELISA). Here, we show (i) a soybean KTI abrogates LPS-induced up-regulation of TNF-alpha mRNA and protein expression in a dose-dependent manner in gingival fibroblasts, (ii) KTI also blocks the induction of TNF-alpha target molecules interleukin-1beta (IL-1beta) and IL-6 proteins, (iii) inhibition by KTI of TNF-alpha induction correlates with the suppressive capacity of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 signaling pathways, implicating repressed ERK1/2 and p38 signalings in the inhibition, and (iv) pretreatment of cells with KTI blocked LPS-induced nuclear factor kappaB (NFkappaB) activation. Our results indicate that KTI inhibits LPS-induced up-...Continue Reading

Mentioned in this Paper

Tumor Cells, Uncertain Whether Benign or Malignant
Biochemical Pathway
Necrosis
Alpha-1-microglobulin
Tumor Necrosis Factor-alpha
Specimen Type - Fibroblasts
MAPK3 wt Allele
Trypsin Inhibitors
Mitogen-Activated Protein Kinases
Interdental Papilla

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