Interferon α2b increases MMP-13 and IL-10 expression in Kupffer cells through MAPK signaling pathways.

Hepato-gastroenterology Pub Date : 2015-03-01
Zheng Yu, Man Xie, Xu Fan, Jidong Jia
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引用次数: 0

Abstract

Background/aims: Kupffer cells play critical roles in both progression and resolution of liver fibrosis. Interferon α2b is an important immunoregulator which has anti-fibrotic effect in addition to its antiviral effect. It remained unclear whether the anti-fibrotic effect of interferon α2b is mediated by regulating functions of Kupffer cells.

Methodology: Primary isolated Kupffer cells were cultured with interferon α2b and the expression of matrix metalloproteinase-13, interleukin-10, transforming growth factor -β1 and tumor necrosis factor-α were measured. To investigate the role of mitogen-activated protein kinase pathways in regulating cytokines production by interferon α2b-stimulated Kupffer cells, inhibitors were given before cells were treated with interferon a2b.

Results: Cell purity was more than 98%. Stimulating Kupffer cells with interferon α2b led to a dramatic increase in matrix metalloproteinase-13 and interleukin-10 expression. In contrast, the values of tumor necrosis factor-α and transforming growth factor -β1 remained unchanged throughout the 24-hour observation period. Inhibited ERK1/2 pathway prevented interferon α2b-triggered matrix metalloproteinase-13 production, while inhibited p38MAPK, ERK1/2 or JNK signaling pathways all blocked interleukin-10 expression.

Conclusions: Interferon α2b may exert anti-fibrotic effect by elevating the level of matrix metalloproteinase-13 and interleukin-10 in Kupffer cells, in a mitogen-activated protein kinase signaling pathways-dependent manner.

干扰素α2b通过MAPK信号通路增加Kupffer细胞中MMP-13和IL-10的表达。
背景/目的:库普弗细胞在肝纤维化的进展和消退中起关键作用。干扰素α2b是一种重要的免疫调节剂,除具有抗病毒作用外,还具有抗纤维化作用。干扰素α2b的抗纤维化作用是否通过调节Kupffer细胞的功能介导尚不清楚。方法:用干扰素α2b培养原代离体Kupffer细胞,检测基质金属蛋白酶-13、白细胞介素-10、转化生长因子-β1、肿瘤坏死因子-α的表达。为了研究丝裂原激活的蛋白激酶途径在干扰素α2b刺激的Kupffer细胞产生细胞因子中的作用,在干扰素a2b处理细胞之前给予抑制剂。结果:细胞纯度大于98%。干扰素α2b刺激Kupffer细胞可显著增加基质金属蛋白酶-13和白细胞介素-10的表达。而肿瘤坏死因子-α和转化生长因子-β1在24小时的观察期内没有变化。抑制ERK1/2通路可阻止干扰素α2b触发的基质金属蛋白酶-13的产生,而抑制p38MAPK、ERK1/2或JNK信号通路均可阻断白细胞介素-10的表达。结论:干扰素α2b可能通过上调Kupffer细胞中基质金属蛋白酶-13和白细胞介素-10的水平发挥抗纤维化作用,其机制依赖于丝裂原激活的蛋白激酶信号通路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hepato-gastroenterology
Hepato-gastroenterology 医学-外科
自引率
0.00%
发文量
1
审稿时长
1.9 months
期刊介绍: Hepato-Gastroenterology has been discontinued as of 2015. Extremely limited quantities of back issues in print available for sale.
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