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Increased chemokine (C–C motif) ligand 21 expression and its correlation with osteopontin in Graves’ disease

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Abstract

Graves’ disease (GD) is a chronic autoimmune process characterized by the production of auto-antibodies that presumably consequent to the lymphocytic infiltrates in the thyroid. Chemokine (C–C motif) ligand 21 (CCL21) is important for the circulation of CC-chemokine receptor 7 (CCR7)-expressing cells. Meanwhile, osteopontin (OPN) enhances the production of proinflammatory cytokines and chemokines through NF-κB and MAPK signaling pathways in GD. Although CCL21 has been reported to play a vital role in several autoimmune diseases, little is known about the relationship between CCL21 and GD development. This study aimed to detect the CCL21 level in GD and to examine the role of OPN in regulating CCL21 production. 40 initial GD patients, 15 euthyroid GD patients, 12 TRAb-negative GD patients, and 25 healthy control donors were recruited. CCL21 levels in plasma and culture supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). CD4+ T cells were isolated from peripheral blood mononuclear cells using antibody-coated magnetic beads. Quantitative polymerase chain reaction was used to determine CCL21 expression levels in CD4+ T cells. We demonstrated for the first time that plasma CCL21 levels were overexpressed in GD patients and recovered in TRAb-negative GD patients. Moreover, CCL21 levels correlated with TRAb levels and plasma OPN concentrations. Furthermore, we demonstrated that recombinant OPN increased the expression of CCL21 in a dose- and time-dependent manner. These data indicated a clinical correlation between plasma CCL21 levels and GD. CCL21 could serve as a novel biomarker for GD as well as a potential target for TRAb-positive GD treatment.

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Acknowledgments

This study was supported by the Grants from the National Natural Science Foundation of China (No. 81270872), Shanghai Municipal Natural Science Foundation (No. 11495803400), the Sector Funds of Ministry of Health (No. 201002002, No. 201202008), and The National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology (No. 2012ZX09303006-001).

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    Authors and Affiliations

    1. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China

      Yicheng Qi, Xiaoli Li, Qianwei Zhang, Fengjiao Huang, Yulin Zhou, Jie Hong, Bin Cui, Weiqing Wang, Guang Ning & Shu Wang

    2. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chongqing Road, Shanghai, 200025, China

      Yicheng Qi, Xiaoli Li, Qianwei Zhang, Bin Cui, Guang Ning & Shu Wang

    3. Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital Affiliated Shanghai Jiao-Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China

      Dongping Lin

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    1. Yicheng Qi
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    Correspondence to Guang Ning or Shu Wang.

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    Yicheng Qi, Xiaoli Li, and Qianwei Zhang contributed equally to this work.

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    Qi, Y., Li, X., Zhang, Q. et al. Increased chemokine (C–C motif) ligand 21 expression and its correlation with osteopontin in Graves’ disease. Endocrine 50, 123–129 (2015). https://doi.org/10.1007/s12020-015-0552-7

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    • DOI: https://doi.org/10.1007/s12020-015-0552-7

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