Activation of the IL-6/JAK2/STAT3 pathway induces plasma cell mastitis in mice

作者：Liu, Yang; Zhang, Jian; Zhou, Yu-hui; Zhang, Hui-min; Wang, Ke; Ren, Yu; Jiang, Yi-na; Han, Shui-ping; He, Jian-jun^*; Tang, Xiao-jiang^*

来源：Cytokine, 2018, 110: 150-158.

DOI：10.1016/j.cyto.2018.05.002

• Plasma cell mastitis
• IL-6/JAK2/STAT3 pathway
• Mouse model
• Pathogenesis

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.

• 出版日期2018-10
• 单位西安交通大学