Role of IL-17A in Neutrophil Recruitment and Hepatic Injury after Warm Ischemia-Reperfusion Mice
Role of IL-17A in Neutrophil Recruitment and Hepatic Injury after Warm Ischemia-Reperfusion Mice
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DOI：
10.4049/jimmunol.1100490
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发表时间：
2011-11-01
影响因子：
4.4
通讯作者：
Hara, Michio
中科院分区：
文献类型：
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作者：
Kono, Hiroshi;Fujii, Hideki;Hara, Michio
最近的证据表明，IL-17A调节中性粒细胞依赖性器官损伤。因此，本研究的目的是确定IL-17A在缺血再灌注（I/R）后中性粒细胞募集和随后的肝损伤中的作用。对野生型和IL-17A敲除小鼠两种小鼠模型进行I/R损伤评估。夹持肝内侧最大叶90分钟。在另一组实验中，在I/R前给敲除小鼠注射重组小鼠（rm） IL-17A同型二聚体或rmIL-17A/F异源二聚体，观察肝损伤。分离的Kupffer细胞与rmIL-17A或rmIL-17F孵育，并测量tnf - α的产生。通过血清转氨酶水平评估肝损伤程度的研究表明，这两种模型在急性期（6小时）的水平相似。相比之下，在I/R后的亚急性期（20 h），与野生型小鼠相比，敲除小鼠的血清转氨酶水平和肝坏死百分比均显著降低。在基因敲除小鼠中观察到的肝损伤的减少与趋化因子和粘附分子表达的抑制以及中性粒细胞向肝脏浸润的减少有关。在I/R亚急性期，给予IL-17A同型二聚体，而不给予IL-17A/F异源二聚体，会增加KO小鼠的肝损伤。与rmIL-17F相比，与rmIL-17A孵育的细胞中分离的Kupffer细胞产生的tnf - α显著增加。这些结果表明，IL-17A是在再灌注后亚急性期启动中性粒细胞诱导的炎症反应和肝损伤的关键调节因子。中华免疫学杂志，2011,18(7):818- 825。
Recent evidence suggests that IL-17A regulates neutrophil-dependent organ injury. Accordingly, the purpose of this study was to determine the role of IL-17A in neutrophil recruitment after ischemia-reperfusion (I/R) and in subsequent liver injury. Two mouse models including wild-type and IL-17A knockout mice were evaluated for I/R injury. The medial largest lobe of the liver was clamped for 90 min. In another set of experiments, recombinant mouse (rm) IL-17A homodimer or rmIL-17A/F heterodimer were administered to knockout mice before I/R, and liver injury was investigated. Isolated Kupffer cells were incubated with rmIL-17A or rmIL-17F, and production of TNF-alpha was measured. Studies evaluating the extent of liver injury as measured by serum transaminase levels demonstrated similar levels in the acute phase (6 h) in these two models. In contrast, in the subacute phase (20 h) after I/R, both serum transaminase levels and percent of hepatic necrosis were significantly reduced in the knockout mice compared with the wild-type mice. This reduction in liver injury seen in the knockout mice was associated with suppression of chemokine and adhesion molecule expression and reduction in infiltration of neutrophils into the liver. Administration of rmIL-17A homodimer, but not IL-17A/F heterodimer, increased liver injury in the subacute phase of I/R in KO mice. TNF-alpha production by isolated Kupffer cells increased significantly in the cells incubated with rmIL-17A compared with rmIL-17F. These results indicate that IL-17A is a key regulator in initiating neutrophil-induced inflammatory responses and hepatic injury in the subacute phase after reperfusion. The Journal of Immunology, 2011, 187: 4818-4825.