1. B7-H3 participates in human salivary gland epithelial cells apoptosis through NF-κB pathway in primary Sjögren's syndrome.
- Author
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Li P, Yang Y, Jin Y, Zhao R, Dong C, Zheng W, Zhang T, Li J, and Gu Z
- Subjects
- Aquaporin 5 metabolism, B7 Antigens blood, Case-Control Studies, Cell Proliferation, Humans, Middle Aged, Sjogren's Syndrome blood, Apoptosis, B7 Antigens metabolism, Epithelial Cells metabolism, Epithelial Cells pathology, NF-kappa B metabolism, Salivary Glands pathology, Sjogren's Syndrome metabolism, Sjogren's Syndrome pathology
- Abstract
Background: Primary Sjögren's syndrome (pSS) is an autoimmune disorder mainly characterized by exocrine gland injury. Costimulatory molecules play an important role in immune-regulatory networks. Although B7 family costimulatory molecules were previously discovered in human salivary gland epithelial (HSGE) cells in pSS, the effects of the B7 family member B7-H3 (CD276) have not been well elucidated. Thus, this study aimed to investigate the role and mechanism of B7-H3 in HSGE cells in pSS., Methods: The expression of B7-H3, B7-H1, PD-1 in serum, saliva and salivary gland were examined by immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to test the expression and distribution of B7-H3, AQP5 and CK-8 in salivary gland tissues. Flow cytometry, Cell Counting Kit 8 (CCK-8) and western blot (WB) were performed to research the apoptotic, proliferative and inflammatory effects of B7-H3 in primary HSGE cells and HSGE cell lines., Results: Our results showed that the expression of PD-1, B7-H1 and B7-H3 in peripheral blood, and salivary glands in pSS patients was higher than that in healthy controls, which was positive correlation with the grade of the salivary glands. The expression of B7-H3 in saliva was higher in pSS patients than that in healthy controls, which was detected with the most significant difference of them. The expression of B7-H3 in primary HSGE cells of pSS patients was significantly higher than healthy controls. B7-H3 increased activity of NF-κB pathway and promoted inflammation of HSGE cells, decreasing the expression of AQP5. Furthermore, B7-H3 overexpression inhibited proliferation and induced apoptosis in HSGE cell lines., Conclusion: B7-H3 could promote inflammation and induce apoptosis of HSGE cells by activating NF-κB pathway, which might be a promising therapeutic target for pSS.
- Published
- 2019
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