Activation of the IL-6/JAK2/STAT3 pathway induces plasma cell mastitis in mice
Activation of the IL-6/JAK2/STAT3 pathway induces plasma cell mastitis in mice
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DOI：
10.1016/j.cyto.2018.05.002
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发表时间：
2018-10-01
期刊：
影响因子：
3.8
通讯作者：
Tang, Xiao-jiang
中科院分区：
文献类型：
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作者：
Liu, Yang;Zhang, Jian;Tang, Xiao-jiang
浆细胞性乳腺炎（PCM）是一种治疗方法有限且易复发的慢性乳腺炎。PCM的组织病理学特征是乳腺导管周围浸润大量浆细胞。我们之前的研究表明，IL-6/STAT3信号通路的活性在PCM患者中升高。然而，PCM的病因仍不清楚。在本研究中，我们试图探讨IL-6/JAK2/STAT3信号通路在PCM发病机制中的作用。组织学分析表明，接受人乳腺组织匀浆后注射IL-6的小鼠乳腺表现出与人乳腺组织相似的PCM特征。PCM小鼠乳腺CD138 +浆细胞中IL-6/JAK2/STAT3信号活性显著升高，Bcl-2高表达。此外，用JAK家族激酶抑制剂AG-490治疗可抑制IL-6/JAK2/STAT3信号级联的激活，从而导致乳腺浆细胞数量减少，逆转PCM的发病机制。综上所述，我们的研究表明，通过将IL-6注射到接受人乳腺组织匀浆的小鼠乳腺中，激活IL-6/JAK2/STAT3通路，成功建立了PCM小鼠模型。因此，IL-6/JAK2/STAT3信号通路在协调PCM的发病机制中起着关键作用。
Plasma cell mastitis (PCM) is a chronic mastitis with limited treatment options and common recurrence. A histopathological hallmark of PCM is the infiltration of numerous plasma cells surrounding the mammary duct. Our previous study showed that the activity of the IL-6/STAT3 signaling pathway was elevated in patients with PCM. However, the etiology of PCM remains largely unclear. In this study, we sought to explore the effects of IL-6/JAK2/STAT3 signaling pathway in the pathogenesis of PCM. Histological analysis showed that the mammary glands of mice that received human breast tissue homogenates, followed by an injection of IL-6, exhibited features of PCM similar to human PCM. The IL-6/JAK2/STAT3 signaling activity was significantly elevated and Bcl-2 was highly expressed in CD138 + plasma cells in the mammary glands of mice with PCM. Furthermore, treatment with AG-490, an inhibitor of JAK family kinases, suppressed activation of the IL-6/JAK2/STAT3 signaling cascade, in turn resulting in a decreased number of plasma cells in the mammary gland and reversing the pathogenesis of PCM. Taken together, our study indicated that a PCM mouse model was successfully established through activation of the IL-6/JAK2/STAT3 pathway by injecting IL-6 into the mammary gland of mouse that had received homogenates of human breast tissue. Thus, the IL-6/JAK2/STAT3 signaling pathway plays a critical role in orchestrating the pathogenesis of PCM.