Glycyrrhizin, a direct HMGB1 antagonist, ameliorates inflammatory infiltration in a model of autoimmune thyroiditis via inhibition of TLR2-HMGB1 signaling.

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Glycyrrhizin, a direct HMGB1 antagonist, ameliorates inflammatory infiltration in a model of autoimmune thyroiditis via inhibition of TLR2-HMGB1 signaling.

Thyroid. 2017 Mar 31;:

Authors: Li C, Peng S, Liu X, Han C, Wang X, Jin T, Liu S, Wang W, Xie X, He X, Zhang H, Shan L, Fan C, Shan Z, Teng W

Abstract
Background：High mobility group box-1(HMGB1), a non-histone protein, plays an important role in autoimmune diseases. However, the significance of HMGB1 in the pathogenesis of autoimmune thyroiditis has not been reported. The purpose of this study was to explore whether HMGB1 is participated in the progress of autoimmune thyroiditis and glycyrrhizin(GL), a direct inhibitor of HMGB1, relieves the severity of thyroid inflammatory infiltration in a murine model of autoimmune thyroiditis.
METHODS: A total of 80 male NOD.H-2h4 mice were randomly divided into control or iodine supplement (NaI) group at 4 weeks of age, and control group was fed with regular water, NaI group was supplied with 0.005% sodium iodine water. Another 24 male NOD.H-2h4 mice were also randomized into 3 groups (n=8 per group) as follows: control, NaI and GL treatment after iodine supplement (NaI+GL). The NOD.H-2h4 mice were fed with 0.005% sodium iodide water for 8 weeks to enhance autoimmune thyroiditis. After iodine treatment, the mice received intraperitoneal injections of glycyrrhizin for 4 weeks. The severity of lymphocytic infiltration in the thyroid gland was measured by histopathological study. The serum levels of HMGB1, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β) and thyroglobulin antibody (TgAb) titers were measured using enzyme linked immunosorbent assay. HMGB1 expression was measured via immunohistochemical staining and Real-Time PCR. TLR2, HMGB1, MyD88 and NF-B were measured by Western blot.
RESULTS: The mRNA expression of HMGB1 was significantly higher at 8 and 16 weeks in NaI group than in control group. Serum levels of TgAb, HMGB1, TNF-α, IL-6, IL-1β were significantly increased in NaI group, but were dramatically attenuated with GL injection. The prevalence of thyroiditis and the infiltration of lymphocytes were significantly decreased in NaI+GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and NF-B in thyroid gland and attenuated the severity of thyroiditis.
CONCLUSION: HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. Glycyrrhizin effectively attenuated thyroiditis in the iodine-induced NOD.H-2h4 mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.

PMID: 28363255 [PubMed - as supplied by publisher]

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