Disparate expression of IL-12 by SJL/J and B10.S macrophages during Theiler's virus infection is associated with activity of TLR7 and mitogen-activated protein kinases
Disparate expression of IL-12 by SJL/J and B10.S macrophages during Theiler's virus infection is associated with activity of TLR7 and mitogen-activated protein kinases
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DOI：
10.1016/j.micinf.2004.10.014
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发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Petro, TM
中科院分区：
文献类型：
--
作者：
Petro, TM
SJL/J小鼠和B10.S小鼠对泰勒氏小鼠脑脊髓炎病毒(TMEV)易感性的差异可能是先天抗病毒免疫反应成分差异的原因。其中，IL-12、干扰素-β、Toll样受体3(TLR3)、TLR7的表达。并对感染TMEV的SJL/J和B10.S巨噬细胞的丝裂原活化蛋白(MAP)-激酶进行了检测。感染后24小时，SJL/J巨噬细胞的TMEV RNA、IL-12 p40和TLR3水平高于B10.S巨噬细胞，而IL-12 p70和IL-12 p35亚基水平低于B10.S巨噬细胞。外源性IL-12p70或干扰素-P可增强SJL/J巨噬细胞对TMEV感染的抵抗力。在TMEV感染前，用p38 MAP-K抑制剂SB203580或细胞外信号调节蛋白激酶(ERK)MAP-K抑制剂U0126预处理巨噬细胞，以评估MAP-K。U0126降低SJL/J，但增加B10.S巨噬细胞IL-12p40和p70的表达。U0126可降低SJL/J巨噬细胞的IL-12p35反应。为评价TLR7、SJL/J和B10，用TLR7配体洛索里宾刺激S-巨噬细胞。洛索里宾诱导B10.S巨噬细胞产生IL-12p70和表达p35的作用明显高于SJL/J巨噬细胞。U0126可增强洛克索滨诱导的B10.S巨噬细胞IL-12p40和IL-12p70的表达，但对SJL/J巨噬细胞无明显影响。因此，SJL/J和B10.S巨噬细胞对TMEV的天然免疫差异可能是由于p35亚基的表达和TLR7的活性以及ERK MAP-Kase下游因子的激活导致的IL-12p70产生的差异。(C)2005年爱思唯尔集团。版权所有。
Differences in components of innate anti-viral immune responses may account for the contrast in susceptibility to Theiler's murine encephalomyelitis virus (TMEV) between SJL/J and B10.S mice. Herein, the expression of IL-12, interferon (IFN)-beta, Toll-like receptors 3 (TLR3) TLR7. and mitogen-activated protein (MAP)-kinases was evaluated in SJL/J and B10.S macrophages infected with TMEV. Twenty-four hours after infection, SJL/J macrophages exhibited higher levels of TMEV RNA, IL-12 p40, and TLR3 but lower levels of IL-12 p70 and the IL-12 p35 subunit compared with B10.S macrophages. Addition of exogenous IL-12 p70 or IFN-P increased the resistance of SJL/J macrophages to TMEV infection. To assess MAP-kinases, macrophages were pretreated with the p38 MAP-kinase inhibitor SB203580 or extracellular signal-regulated kinases (ERK) MAP-kinase inhibitor U0126 before TMEV infection. U0126 reduced SJL/J but increased B10.S macrophage expression of IL- 12 p40 and p70 in response to TMEV. U0126 decreased the IL- 12 p35 response of SJL/J macrophages. To assess TLR7, SJL/J and B10.S macrophages were stimulated with loxoribine, a TLR7 ligand. Loxoribine induced more IL-12 p70 production and p35 expression in B10.S than SJL/J macrophages. U0126 increased loxoribine-induced expression of IL-12 p40 and IL- 12 p70 in B10.S but not SJL/J macrophages. Thus, differences in production of IL-12 p70 due to expression of the p35 subunit and in activity of TLR7, as well as activation of factors downstream of ERK MAP-kinases likely underlie the disparity in innate immunity between SJL/J and B10.S macrophages to TMEV. (c) 2005 Elsevier SAS. All rights reserved.