Yu Lili, Yan Keqin, Liu Peng, Li Nan, Liu Zhenghui, Zhu Weiwei, Chen Yongmei, Han Daishu
Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China.
Immunol Cell Biol. 2014 Feb;92(2):105-15. doi: 10.1038/icb.2013.66. Epub 2013 Oct 29.
Although wide range of viruses can infect adipose tissues, innate antiviral response of adipose cells has not been investigated. This study focused on innate antiviral system in mouse adipose cells. Major virus sensors including Toll-like receptor 3 (TLR3), melanoma differentiation-associated antigen 5 (MDA5) and retinoic acid-inducible gene I (RIG-I) are constitutively expressed in preadipocytes and adipocytes. Poly(I:C), a common agonist of TLR3, MDA5 and RIG-I, induced the expression of type I interferons (IFN-α/β) in the two types of adipose cells through the activation of IFN-regulatory factor 3 and upregulated pro-inflammatory factors such as TNF-α and IL-6 through the activation nuclear factor kappa B. Moreover, poly(I:C) induced multiple antiviral proteins including IFN-stimulating gene 15, 2'5'-oligoadenylate synthetase and Mx GTPase 1 in preadipocytes and adipocytes. The poly(I:C)-induced innate antiviral response was reduced by TLR3 deficiency and knockdown of MDA5 or RIG-I. Poly(I:C) also inhibited the differentiation of preadipocytes to adipocytes and suppressed the expression of leptin, adiponectin and resistin in mature adipocytes. The results demonstrated that adipose cells are equipped with innate antiviral system, which may modulate the function of adipocytes.
尽管多种病毒可感染脂肪组织,但脂肪细胞的先天性抗病毒反应尚未得到研究。本研究聚焦于小鼠脂肪细胞中的先天性抗病毒系统。主要的病毒传感器,包括Toll样受体3(TLR3)、黑色素瘤分化相关抗原5(MDA5)和视黄酸诱导基因I(RIG-I),在前脂肪细胞和脂肪细胞中组成性表达。多聚肌苷酸胞苷酸(Poly(I:C))是TLR3、MDA5和RIG-I的常见激动剂,通过激活干扰素调节因子3诱导这两种脂肪细胞中I型干扰素(IFN-α/β)的表达,并通过激活核因子κB上调促炎因子如肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)。此外,Poly(I:C)在前脂肪细胞和脂肪细胞中诱导多种抗病毒蛋白,包括干扰素刺激基因15、2',5'-寡腺苷酸合成酶和Mx鸟苷三磷酸酶1。TLR3缺陷以及MDA5或RIG-I的敲低会降低Poly(I:C)诱导的先天性抗病毒反应。Poly(I:C)还抑制前脂肪细胞向脂肪细胞的分化,并抑制成熟脂肪细胞中瘦素、脂联素和抵抗素的表达。结果表明,脂肪细胞具备先天性抗病毒系统,该系统可能调节脂肪细胞的功能。