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  • 1
    ISSN: 1600-0765
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Cytokines are produced as a consequence of photo-damaged DNA and oxidative stress in ultraviolet (UV)-exposed keratinocytes. A soybean Kunitz trypsin inhibitor (KTI) down-regulates the expression of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) in tumor cells and inflammatory cells.Aim:  The effect of KTI on TNF-α production in UV-exposed primary human keratinocytes was analyzed.Results:  We show (i) UV induced up-regulation of TNF-α mRNA and protein expression in keratinocytes; (ii) cells treated with KTI before UV irradiation showed a significantly lower accumulation of TNF-α protein in a dose-dependent manner and a reduced UV-induced up-regulation of TNF-α mRNA expression; (iii) KTI inhibited the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins; (iv) UV irradiation transiently activated c-Jun N-terminal kinase (JNK) and Akt signaling but only weakly activated extracellular signal-regulated kinase (ERK) and p38; (v) KTI specifically inhibited UV-induced activation of ERK, JNK, and p38, but not Akt; (vi) treatment of cells with SP600125, a pharmacological inhibitor of JNK, predominantly suppressed UV-induced up-regulation of TNF-α expression; and (vii) KTI did not enhance suppression of UV-induced JNK phosphorylation by SP600125.Conclusions:  KTI specifically inhibited UV-induced up-regulation of cytokine expression predominantly through suppression of JNK signaling pathway.
    Type of Medium: Electronic Resource
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