Dataset Information

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-α, 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

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

Kim Ji-Won JW Kim Sung-Min SM Park Jin-Sil JS Hwang Sun-Hee SH Choi JeongWon J Jung Kyung-Ah KA Ryu Jun-Geol JG Lee Seon-Yeong SY Kwok Seung-Ki SK Cho Mi-La ML Park Sung-Hwan SH

Arthritis research & therapy 20190604 1

<h4>Background</h4>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.<h4>Methods</h4>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 w ...[more]

PMID: 31164166

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