IL-13 Orchestrates Resolution of Chronic Intestinal Inflammation via Phosphorylation of Glycogen Synthase Kinase-3β
IL-13 Orchestrates Resolution of Chronic Intestinal Inflammation via Phosphorylation of Glycogen Synthase Kinase-3β
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DOI：
10.4049/jimmunol.1301072
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发表时间：
2014-04-15
影响因子：
4.4
通讯作者：
Schlitt, Hans J.
中科院分区：
文献类型：
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作者：
Fichtner-Feigl, Stefan;Kesselring, Rebecca;Schlitt, Hans J.
炎症的自发改善（通常伴有纤维化）是许多慢性炎症过程的众所周知但知之甚少的结果。我们在慢性三硝基苯磺酸诱导的结肠炎模型中研究了这一现象，这是一种小鼠实验性结肠炎，尽管持续三硝基苯磺酸刺激，但我们最终发现其自发消退。对该解决机制的分析表明，它严重依赖于IL-13对STAT 6的激活，随后是糖原合成酶激酶-3 δ的磷酸化（失活），至少部分地通过STAT 6对p38 MAPK的诱导。这种糖原合酶激酶-3 δ失活导致CREB和p65 DNA结合活性的变化，这有利于减少促炎性IL-17的产生和增加抗炎性IL-10的产生。因此，在这种情况下，IL-13作为一个分子开关，导致炎症的解决。
Spontaneous amelioration of inflammation (often accompanied by fibrosis) is a well-known, but poorly understood, outcome of many chronic inflammatory processes. We studied this phenomenon in a chronic trinitrobenzene sulfonic acid-induced colitis model, an experimental colitis in mice that we showed to ultimately undergo spontaneous resolution, despite continued trinitrobenzene sulfonic acid stimulation. Analysis of the mechanism of this resolution revealed that it was critically dependent on IL-13 activation of STAT6, followed by phosphorylation (inactivation) of glycogen synthase kinase-3 delta, at least in part via STAT6 induction of p38 MAPK. Such glycogen synthase kinase-3 delta inactivation causes changes in CREB and p65 DNA-binding activity that favors decreased proinflammatory IL-17 production and increased anti-inflammatory IL-10 production. Thus, in this case, IL-13 acts as a molecular switch that leads to resolution of inflammation.