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Cytokine. 2018 Oct;110:150-158. doi: 10.1016/j.cyto.2018.05.002. Epub 2018 May 9.

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

Author information

1
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China.
2
Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China.
3
Department of Pathology, School of Medicine, Xi'an Jiaotong University, No. 76, West Yanta Road, Xi'an 710061, Shaanxi Province, China.
4
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China. Electronic address: chinahjj@163.com.
5
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, No. 277, West Yanta Road, Xi'an 710061, Shaanxi Province, China. Electronic address: jdyfytxj@163.com.

Abstract

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.

KEYWORDS:

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

PMID:
29751177
DOI:
10.1016/j.cyto.2018.05.002

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