一种大豆Kunitz胰蛋白酶抑制剂可降低紫外线照射的原代人角质形成细胞中肿瘤坏死因子-α的产生。

A soybean Kunitz trypsin inhibitor reduces tumor necrosis factor-alpha production in ultraviolet-exposed primary human keratinocytes.

作者信息

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

机构信息

Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Handayama, Hamamatsu, Shizuoka, Japan.

出版信息

Exp Dermatol. 2005 Oct;14(10):765-74. doi: 10.1111/j.1600-0625.2005.00359.x.

DOI:10.1111/j.1600-0625.2005.00359.x

PMID:16176285

Abstract

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-alpha (TNF-alpha) in tumor cells and inflammatory cells.

AIM

The effect of KTI on TNF-alpha production in UV-exposed primary human keratinocytes was analyzed.

RESULTS

We show (i) UV induced up-regulation of TNF-alpha mRNA and protein expression in keratinocytes; (ii) cells treated with KTI before UV irradiation showed a significantly lower accumulation of TNF-alpha protein in a dose-dependent manner and a reduced UV-induced up-regulation of TNF-alpha mRNA expression; (iii) KTI inhibited the induction of TNF-alpha target molecules interleukin-1beta (IL-1beta) 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-alpha 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.

摘要

背景

细胞因子是紫外线（UV）照射的角质形成细胞中DNA光损伤和氧化应激的产物。大豆Kunitz胰蛋白酶抑制剂（KTI）可下调肿瘤细胞和炎症细胞中促炎细胞因子如肿瘤坏死因子-α（TNF-α）的表达。

目的

分析KTI对紫外线照射的原代人角质形成细胞中TNF-α产生的影响。

结果

我们发现（i）紫外线诱导角质形成细胞中TNF-α mRNA和蛋白表达上调；（ii）紫外线照射前用KTI处理的细胞，TNF-α蛋白的积累以剂量依赖方式显著降低，且紫外线诱导的TNF-α mRNA表达上调受到抑制；（iii）KTI抑制TNF-α靶分子白细胞介素-1β（IL-1β）和IL-6蛋白的诱导；（iv）紫外线照射可短暂激活c-Jun氨基末端激酶（JNK）和Akt信号通路，但仅微弱激活细胞外信号调节激酶（ERK）和p38；（v）KTI特异性抑制紫外线诱导的ERK、JNK和p38激活，但不抑制Akt；（vi）用JNK的药理抑制剂SP600125处理细胞，主要抑制紫外线诱导的TNF-α表达上调；（vii）KTI不会增强SP600125对紫外线诱导的JNK磷酸化的抑制作用。