Metformin improves salivary gland inflammation and hypofunction in murine Sjogren's syndrome.

ABSTRACT:

Background

Activated T and B cells participate in the development and progression of Sjögren's syndrome (SS). Metformin, a first-line anti-diabetic drug, exerts anti-inflammatory and immunomodulatory effects by activating AMPK. We investigated the therapeutic effect of metformin in non-obese diabetic (NOD)/ShiLtJ mice, an animal model of SS.

Methods

Metformin or vehicle was administered orally to the mice for 9?weeks. The salivary flow rate was measured at 11, 13, 15, 17, and 20?weeks. Histological analysis of the salivary glands from vehicle- and metformin-treated mice was conducted. CD4⁺ T and B cell differentiation in the peripheral blood and/or spleen was determined by flow cytometry. Serum total IgG, IgG1, and IgG2a levels were determined by enzyme-linked immunosorbent assay.

Results

Metformin reduced salivary gland inflammation and restored the salivary flow rate. Moreover, metformin reduced the interleukin (IL)-6, tumor necrosis factor-?, IL-17 mRNA, and protein levels in the salivary glands. Metformin reduced the Th17 and Th1 cell populations and increased the regulatory T cell population in the peripheral blood and spleen and modulated the balance between Tfh and follicular regulatory T cells. In addition, metformin reduced B cell differentiation into germinal center B cells, decreased the serum immunoglobulin G level, and maintained the balance between IL-10- and IL-17-producing B cells.

Conclusion

Metformin suppresses effector T cells, induces regulatory T cells, and regulates B cell differentiation in an animal model of SS. In addition, metformin ameliorates salivary gland inflammation and hypofunction, suggesting that it has potential for the treatment of SS.

SUBMITTER: Kim JW 

PROVIDER: S-EPMC6549273 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature