Glutathione Trisulfide Prevents Lipopolysaccharide-induced Inflammatory Gene Expression in Retinal Pigment Epithelial Cells
Glutathione Trisulfide Prevents Lipopolysaccharide-induced Inflammatory Gene Expression in Retinal Pigment Epithelial Cells
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DOI：
10.1080/09273948.2020.1833224
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发表时间：
2020-11
影响因子：
3.3
通讯作者：
Hiroshi Tawarayama;Noriyuki Suzuki;Maki Inoue-Yanagimachi;Noriko Himori;Satoru Tsuda;Kota Sato;T. Ida;T. Akaike;H. Kunikata;T. Nakazawa
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文献类型：
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作者：
Hiroshi Tawarayama;Noriyuki Suzuki;Maki Inoue-Yanagimachi;Noriko Himori;Satoru Tsuda;Kota Sato;T. Ida;T. Akaike;H. Kunikata;T. Nakazawa
摘要我们研究了谷胱甘肽三硫化物（GSSSG）对脂多糖（LPS）诱导的永生化ARPE-19和原代人和小鼠视网膜色素上皮（RPE）细胞中炎症基因表达的影响。GSSSG处理的ARPE-19细胞中的硫烷硫分子显著增加。GSSSG阻止LPS诱导的ARPE-19/原代RPE细胞中白细胞介素（IL）-1β、IL-6和C-C基序趋化因子配体2（CCL 2）的上调。此外，GSSSG还能抑制核因子-κ B p65亚基的活化，并促进细胞外信号调节激酶1/2（ERK 1/2）的活化。ERK 1/2抑制阻止GSSSG介导的LPS诱导的IL-6和CCL 2上调的抑制。此外，ERK 1/2激活阻止了这些基因在GSSSG缺乏的上调。敲低HMOX 1或NRF 2（称为抗氧化基因）在LPS刺激的情况下不影响GSSSG的活性。这些发现表明，GSSSG减弱LPS诱导的炎症基因表达通过ERK信号过度激活，独立于NRF 2/HMOX 1途径。
ABSTRACT We investigated the effects of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammatory gene expression in immortalized ARPE-19, and primary human and mouse retinal pigment epithelial (RPE) cells. Sulfane sulfur molecules were significantly increased in GSSSG-treated ARPE-19 cells. GSSSG prevented the LPS-induced upregulation of interleukin (IL)-1β, IL-6, and C-C motif chemokine ligand 2 (CCL2) in ARPE-19/primary RPE cells. Moreover, GSSSG prevented the activation of the nuclear factor-kappa B p65 subunit, and promoted the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in LPS-treated ARPE-19 cells. ERK1/2 inhibition prevented the GSSSG-mediated inhibition of LPS-induced IL-6 and CCL2 upregulation. Additionally, ERK1/2 activation prevented the upregulation of these genes in the absence of GSSSG. Knockdown of HMOX1 or NRF2, known as anti-oxidative genes, did not affect the activity of GSSSG in the context of LPS stimulation. These findings suggest that GSSSG attenuates LPS-induced inflammatory gene expression via ERK signaling hyperactivation, independently of the NRF2/HMOX1 pathway.