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Suppression of lipopolysaccharide‐induced cytokine production of gingival fibroblasts by a soybean, Kunitz trypsin inhibitor
Author(s) -
Kobayashi Hiroshi,
Yoshida Ryuji,
Kanada Yasufumi,
Fukuda Yoichi,
Yagyu Tatsuo,
Inagaki Kiyokazu,
Kondo Toshiharu,
Kurita Noriyuki,
Suzuki Mika,
Kanayama Naohiro,
Terao Toshihiko
Publication year - 2005
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2005.00824.x
Subject(s) - cytokine , proinflammatory cytokine , tumor necrosis factor alpha , p38 mitogen activated protein kinases , inflammation , mapk/erk pathway , lipopolysaccharide , protein kinase a , kinase , chemistry , western blot , signal transduction , microbiology and biotechnology , biology , endocrinology , immunology , biochemistry , gene
Background: Human bikunin, a Kunitz‐type trypsin inhibitor, inhibits inflammation by down‐regulating the expression of proinflammatory cytokines such as tumor necrosis factor‐alpha (TNF‐α) in tumor cells and inflammatory cells. Objectives: We analyzed the effect of a soybean‐derived Kunitz trypsin inhibitor (KTI) on TNF‐α production in human gingival fibroblasts stimulated by lipopolysaccharide (LPS), an inflammatory inducer. Material and methods: Mitogen‐activated protein kinase (MAPK) activation and cytokine levels were monitored using western blot and a specific enzyme‐linked immunosorbent assay (ELISA). Results: Here, we show (i) a soybean KTI abrogates LPS‐induced up‐regulation of TNF‐α mRNA and protein expression in a dose‐dependent manner in gingival fibroblasts, (ii) KTI also blocks the induction of TNF‐α target molecules interleukin‐1β (IL‐1β) and IL‐6 proteins, (iii) inhibition by KTI of TNF‐α 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 κB (NFκB) activation. Conclusion: Our results indicate that KTI inhibits LPS‐induced up‐regulation of cytokine expression possibly through suppression of ERK1/2 and p38 kinase‐mediated NFκB activation. These findings may identify anti‐inflammatory properties of KTI at the level of gingival fibroblasts and may be relevant to the use of KTI in modulating inflammation, including periodontal disease.