Sulforaphane suppresses polyinosinic-polycytidylic acid-stimulated release of cytokines, chemokines and MMPs by human corneal fibroblasts
Sulforaphane suppresses polyinosinic-polycytidylic acid-stimulated release of cytokines, chemokines and MMPs by human corneal fibroblasts
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萝卜硫素可抑制人角膜成纤维细胞刺激的聚肌胞苷酸、聚胞苷酸释放细胞因子、趋化因子和基质金属蛋白酶。
DOI：
10.3892/mmr.2020.11633
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发表时间：
2020-12-01
影响因子：
3.4
通讯作者：
Liu, Yang
中科院分区：
文献类型：
--
作者：
Liu, Pingping;Liu, Ye;Liu, Yang
病毒性角膜感染是视力障碍和失明的常见原因。多聚肌苷酸-多聚胞苷酸或poly（I：C）在结构上类似于病毒双链RNA，并且与角膜成纤维细胞释放多种细胞因子、趋化因子和基质金属蛋白酶（MMP）有关。萝卜硫素（SFN）是一种存在于十字花科蔬菜中的异硫氰酸酯化合物。本研究探讨了SFN对poly（I：C）刺激的人角膜成纤维细胞（HCFs）释放细胞因子、趋化因子和基质金属蛋白酶（MMPs）的潜在影响。ELISA显示SFN与时间和剂量依赖性地减少poly（I：C）刺激的HCF产生的白细胞介素（IL）-8、趋化蛋白-1、IL-6、MMP-1和MMP-3相关。Western blot分析表明，SFN通过调节丝裂原活化蛋白激酶（MAPK），包括p38和细胞外信号调节激酶（ERK），激活蛋白-1（AP-1）组分c-Jun和激酶Akt，以及核因子（NF）-κ B抑制剂I κ B-α的磷酸化和降解，抑制poly（I：C）的功能。免疫荧光分析显示SFN减弱了poly（I：C）诱导的NF-κ B p65亚基核转位的产生。逆转录-定量PCR分析显示，SFN阻止poly（I：C）诱导的HCF中Toll样受体3（TLR 3）mRNA表达上调。SFN对HCFs无明显细胞毒作用。总之，SFN通过抑制TLR 3、MAPK（p38和ERK）、AP-1、Akt和NF-κ B信号传导，减弱了poly（I：C）诱导的HCF产生促炎趋化因子、细胞因子和MMPs。因此，SFN可能是通过限制免疫细胞浸润来治疗病毒性角膜感染的潜在新疗法。
Viral corneal infection is a common cause of visual impairment and blindness. Polyinosinic-polycytidylic acid, or poly(I:C), is similar to viral double-stranded RNA in structure and has been implicated in the release of a variety of cytokines, chemokines and matrix metalloproteinases (MMPs) by corneal fibroblasts. Sulforaphane (SFN) is an isothiocyanate compound found in cruciferous vegetables. The present study investigated the potential effect of SFN on the poly(I:C)-stimulated release of cytokines, chemokines and MMPs in human corneal fibroblasts (HCFs). ELISA showed that SFN was associated with a time- and dose-dependent reduction in poly(I:C)-stimulated production of interleukin (IL)-8, chemoattractant protein-1, IL-6, MMP-1 and MMP-3 by HCFs. Western blot analysis indicated that SFN suppressed the function of poly(I:C) by modulating mitogen-activated protein kinases (MAPKs), including p38 and extracellular signal-regulated kinase (ERK), activator protein-1 (AP-1) component c-Jun and the kinase, Akt, and the phosphorylation and degradation of the nuclear factor (NF)-kappa B inhibitor I kappa B-alpha. Immunofluorescence analysis revealed that SFN attenuated the production of poly(I:C)-induced nuclear translocation of the NF-kappa B p65 subunit. Reverse transcription-quantitative PCR analysis revealed that SFN prevented the poly(I:C)-induced upregulation of Toll-like receptor 3 (TLR3) mRNA expression in HCFs. No significant cytotoxic effect of SFN on HCFs was observed. In summary, SFN attenuated the poly(I:C)-induced production of proinflammatory chemokines, cytokines and MMPs by HCFs, by inhibiting TLR3, MAPK (p38 and ERK), AP-1, Akt and NF-kappa B signaling. SFN may therefore be a potential novel treatment for viral corneal infection by limiting immune cell infiltration.