Myeloid related proteins are up-regulated in autoimmune thyroid diseases and activate toll-like receptor 4 and pro-inflammatory cytokines in vitro

被引:10
|
作者
Peng, Shiqiao [1 ]
Sun, Xuren [2 ]
Wang, Xinyi [3 ]
Wang, Haoyu [1 ]
Shan, Zhongyan [1 ]
Teng, Weiping [1 ]
Li, Chenyan [1 ]
机构
[1] China Med Univ, Inst Endocrinol, Dept Endocrinol & Metab, Liaoning Prov Key Lab Endocrine Dis,Affiliat Hosp, Shenyang 110001, Liaoning, Peoples R China
[2] China Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Shenyang 110001, Liaoning, Peoples R China
[3] China Med Univ, Affiliated Hosp 1, Dept Lab Med, Shenyang 110001, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
MRP6; MRP8; MRP14; Autoimmune thyroid disease; Calgranulins; Oxidative stress; NEUTROPHIL OXIDATIVE-METABOLISM; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MOLECULAR-PATTERN MOLECULES; GLYCATION END-PRODUCTS; FACTOR-KAPPA-B; GENE-EXPRESSION; HASHIMOTOS-THYROIDITIS; RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD; HUMAN S100A12;
D O I
10.1016/j.intimp.2018.04.009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Purpose: Myeloid-related protein (MRP) family plays an important role in the promotion of cell proliferation and the production of inflammatory cytokines. We investigated the expression of MRP6, MRP8 and MRP14 in thyroid tissues, serum, and peripheral blood monocular cells (PBMCs) in patients with autoimmune thyroid diseases (AITD). Method: The expression of MRP6, MRP8, and MRP14 was investigated using immunohistochemical staining and quantitative real-time polymerase chain reaction in the thyroid glands of 7 patients with Graves' disease (GD), 8 with Hashimoto's thyroiditis (HT), and 7 healthy controls (HC). The serum levels of MRP8/MRP14 complex and MRP6 were investigated in 30 patients with GD, 36 with HT, and 30 with HC. The mRNA expression of MRP proteins in PBMCs was also explored. PBMCs from each group were incubated with MPRs and their effect on Toll-like receptor 4(TLR4) expression and their effect on the levels of the pro-inflammatory cytokines in supernatant were analyzed upon incubating with TLR4 and signaling pathways inhibitors. Results: Serum levels of MRP8/MRP14 and MRP6 were up-regulated in patients with AITD. In addition, mRNA expression of MRP proteins in PBMCs and the thyroid gland was markedly elevated in AITD patients. MRP6 and MPR8 promoted the secretion of TNF-alpha and IL-6 in cultured PBMCs, and this elevation was more pronounced in AITD patients; we also found that this up-regulation was regulated by TLR4/phosphoinositide 3-kinase/nuclear factor-kappa B signaling pathway. Conclusion: The expression of MRP proteins was elevated in AITD patients. Therefore, an MRP-TLR4 dependent signaling may play an important role in the pathogenesis of AITD.
引用
收藏
页码:217 / 226
页数:10
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