IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice
IL-22 exacerbates the severity of CVB3-induced acute viral myocarditis in IL-17A-deficient mice
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IL-22 加剧 IL-17A 缺陷小鼠中 CVB3 诱导的急性病毒性心肌炎的严重程度
DOI：
10.3892/mmr.2013.1323
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发表时间：
2013-04-01
影响因子：
3.4
通讯作者：
Pan, Xiaofen
中科院分区：
文献类型：
--
作者：
Kong, Qing;Xue, Yimin;Pan, Xiaofen
白细胞介素（IL）-22具有促炎或组织保护特性，这取决于受影响组织的性质和局部细胞因子环境，包括IL-17 A共表达的存在或不存在。我们先前已经证明，IL-22在IL-17 A存在下，在患有柯萨奇病毒B3（CVB 3）诱导的急性病毒性心肌炎（AVMC）的小鼠中具有关键的抗炎和抗病毒作用。然而，IL-17 A是否决定了IL-22在AVMC中的功能仍不清楚。因此，本研究，在我们以前的调查的延续，旨在确定是否IL-22发挥明显不同的作用，在缺乏IL-17 A在AVMC使用IL-17 A缺陷型小鼠。结果表明，IL-17 A缺陷小鼠中IL-22的中和减轻了心肌炎的严重程度。这一点通过心脏切片的病理评分和心脏重量/体重（HW/BW）比较低、转录激活因子3（STAT 3）以及促炎细胞因子TNF-α和IL-6的产生减少、随后病毒复制增加和水平降低来证明。抗病毒细胞因子IFN-γ。心脏CVB 3 RNA与IL-22 mRNA和IFN-γ mRNA呈负相关。总之，在没有IL-17 A的情况下，IL-22加重了AVMC的严重程度并抑制了病毒复制。重组IL-17（rIL-17）培养的脾淋巴细胞增加IL-22的产生。结合我们先前的数据，这些结果表明IL-17 A不参与调节抗病毒作用，然而，可能介导IL-22在CVB 3诱导的小鼠AVMC中的组织保护与致病特性。
Interleukin (IL)-22 has either proinflammatory or tissue-protective properties, depending on the nature of the affected tissue and the local cytokine milieu, including the presence or absence of IL-17A co-expression. We have previously demonstrated that IL-22 has critical anti-inflammatory and antiviral roles in mice with coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVMC) in the presence of IL-17A. However, whether IL-17A determines the function of IL-22 in AVMC remains unknown. Therefore, the present study, in continuation of our previous investigations, aimed to determine whether IL-22 plays a distinctly different role in the absence of IL-17A in AVMC by using IL-17A-deficient mice. Results demonstrated that the neutralization of IL-22 in IL-17A-deficient mice alleviated the severity of myocarditis. This was demonstrated by the lower pathological scores of heart sections and ratios of heart weight/body weight (HW/BW), reduced production of activator of transcription 3 (STAT3) and proinflammatory cytokines TNF-alpha and IL-6, followed by increased viral replication and decreased levels of the antiviral cytokine IFN-gamma. Furthermore, the correlation between cardiac CVB3 RNA and IL-22 mRNA or IFN-gamma mRNA was negative. In conclusion, IL-22 exacerbated the severity of AVMC and restrained viral replication in the absence of IL-17A. Spleen lymphocytes cultured with recombinant IL-17 (rIL-17) increased the production of IL-22. Combined with our previous data, these results indicate that IL-17A is not involved in regulating the antiviral role, however, may mediate the tissue-protective versus pathogenic properties of IL-22 in CVB3-induced AVMC in mice.