Department of Medicine and Science of Aging, University G. D'Annunzio-Chieti, Chieti 66100, Italy.
Mar Drugs. 2012 Apr;10(4):890-899. doi: 10.3390/md10040890. Epub 2012 Apr 10.
It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H(2)O(2)), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H(2)O(2), (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments.
已经有人提出，氧化应激会激活各种细胞内信号通路，导致多种促炎细胞因子和趋化因子的分泌。SHP-1 是一种蛋白酪氨酸磷酸酶（PTP），可作为免疫细胞因子信号的负调节剂。然而，细胞内的过氧化氢（H2O2），在刺激时由内源性产生，在环境氧化剂时由外源性产生，已经被认为通过抑制包括 SHP-1 在内的各种 PTP 参与细胞内信号转导过程。在这项研究中，我们研究了虾青素（一种抗氧化海洋类胡萝卜素）在重新建立 U-937 细胞系中 SHP-1 对氧化刺激诱导的促炎细胞因子（IL-1β、IL-6 和 TNF-α）分泌的负调控作用中的潜在作用。ELISA 测量表明，ASTA 处理（10 µM）可减少 H2O2（100 µM）诱导的促炎细胞因子分泌。此外，Western blot 实验表明，这种作用是通过恢复基础 SHP-1 蛋白表达水平和减少 NF-κB（p65）核表达来实现的。
