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Cordycepin Attenuates IFN-γ-Induced Macrophage IP-10 and Mig Expressions by Inhibiting STAT1 Activity in CFA-Induced Inflammation Mice Model.
Inflammation ( IF 4.5 ) Pub Date : 2020-04-01 , DOI: 10.1007/s10753-019-01162-3
Rirong Yang 1 , Xiaoli Wang 1 , Deshuang Xi 1 , Jian Mo 1 , Ke Wang 2 , Shunrong Luo 1 , Jiao Wei 2 , Zhenghua Ren 3 , Hui Pang 2 , Yu Luo 4
Affiliation  

Cordycepin, a natural derivative of adenosine, has been shown to exert pharmacological properties including anti-oxidation, antitumor, and immune regulation. It is reported that cordycepin is involved in the regulation of macrophage function. However, the effect of cordycepin on inflammatory cell infiltration in inflammation remains ambiguous. In this study, we investigated the potential role of cordycepin playing in macrophage function in CFA-induced inflammation mice model. In this model, we found that cordycepin prevented against macrophage infiltration in paw tissue and reduced interferon-γ (IFN-γ) production in both serum and paw tissue. Using luciferase reporter assay, we found that cordycepin suppressed IFN-γ-induced activators of transcription-1 (STAT1) transcriptional activity in a dose-dependent manner. Moreover, western blotting data demonstrated that cordycepin inhibited IFN-γ-induced STAT1 activation through attenuating STAT1 phosphorylation. Further investigations revealed that cordycepin inhibited the expressions of IFN-γ-inducible protein 10 (IP-10) and monokine induced by IFN-γ (Mig), which were the effector genes in IFN-γ-induced STAT1 signaling. Meanwhile, the excessive inflammatory cell infiltration in paw tissue was reduced by cordycepin. These findings demonstrate that cordycepin alleviates excessive inflammatory cell infiltration through down-regulation of macrophage IP-10 and Mig expressions via suppressing STAT1 phosphorylation. Thus, cordycepin may be a potential therapeutic approach to prevent and treat inflammation-associated diseases.

中文翻译:

虫草素通过抑制CFA诱导的炎症小鼠模型中的STAT1活性来减弱IFN-γ诱导的巨噬细胞IP-10和Mig表达。

虫草素是腺苷的天然衍生物,已被证明具有药理特性,包括抗氧化,抗肿瘤和免疫调节。据报道虫草素参与巨噬细胞功能的调节。然而,虫草素对炎症中炎性细胞浸润的作用仍然不清楚。在这项研究中,我们调查了虫草素在CFA诱导的炎症小鼠模型中在巨噬细胞功能中发挥的潜在作用。在该模型中,我们发现虫草素可防止爪子组织中巨噬细胞浸润并降低血清和爪子组织中干扰素-γ(IFN-γ)的产生。使用荧光素酶报告基因测定,我们发现虫草素以剂量依赖的方式抑制了IFN-γ诱导的转录1(STAT1)转录激活因子。此外,免疫印迹数据表明,虫草素通过减弱STAT1磷酸化来抑制IFN-γ诱导的STAT1活化。进一步的研究表明,虫草素抑制了由IFN-γ诱导的STAT1信号转导的效应基因IFN-γ诱导的蛋白10(IP-10)和单因子的表达。同时,虫草素减少了爪组织中过多的炎性细胞浸润。这些发现表明虫草素通过抑制STAT1磷酸化,通过下调巨噬细胞IP-10和Mig表达来减轻过度的炎性细胞浸润。因此,虫草素可能是预防和治疗炎症相关疾病的潜在治疗方法。
更新日期:2020-04-21
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