Activation of the CXCL16/CXCR6 Axis by TNF-α Contributes to Ectopic Endometrial Stromal Cells Migration and Invasion

The activation of systemic and local inflammatory mechanisms, including elevated levels of chemokines and proinflammatory cytokines in endometriosis progression, is becoming more evident in the recent years. Here, we report the involvement of CXC chemokine 16 (CXCL16) and its sole receptor, CXC chemokine receptor 6 (CXCR6), in pathophysiology of endometriosis. Expression of CXCL16, but not CXCR6, was significantly upregulated in endometriotic lesions when compared to control endometrium. Additionally, serum CXCL16 was significantly elevated in women with endometriosis when compared to control group. Moreover, blockade of the CXCL16/CXCR6 axis by CXCR6 small-interfering RNA reduced the migration and invasion of ectopic endometrial stromal cells (EESCs) followed by decreased phosphorylation of ERK1/2. Furthermore, TNF-α treatment induced the expression of CXCL16 in EESCs. In conclusion, these results suggest that CXCL16/CXCR6 axis, whose expression was enhanced by TNF-α, may be associated with the increased motility of EESCs, through regulation of ERK1/2 signaling, thus contributing to the development of endometriosis. These findings indicate that the CXCL16/CXCR6 axis may contribute to the progression of endometriosis and could be served as a potential target for diagnosis and treatment. Similar content being viewed by others

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