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A soybean Kunitz trypsin inhibitor reduces tumor necrosis factor‐α production in ultraviolet‐exposed primary human keratinocytes
Author(s) -
Kobayashi Hiroshi,
Yoshida Ryuji,
Kanada Yasufumi,
Fukuda Yoichi,
Yagyu Tatsuo,
Inagaki Kiyokazu,
Kondo Toshiharu,
Kurita Noriyuki,
Yamada Yoshihiko,
Sado Toshiyuki,
Kitanaka Takashi,
Suzuki Mika,
Kanayama Naohiro,
Terao Toshihiko
Publication year - 2005
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2005.00359.x
Subject(s) - p38 mitogen activated protein kinases , protein kinase b , tumor necrosis factor alpha , proinflammatory cytokine , mapk/erk pathway , kinase , cytokine , signal transduction , protein kinase a , microbiology and biotechnology , chemistry , cancer research , biology , endocrinology , immunology , inflammation
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.