title: CXCR4 antagonist AMD3100 ameliorates thyroid damage in autoimmune thyroiditis in NOD.H‑2h⁴ mice.
abstract: CXC chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor 4 (CXCR4), are upregulated in mice with autoimmune thyroid diseases. However, whether this interaction is involved in the pathophysiology of autoimmune thyroiditis (AIT) remains to be elucidated. In the present study, the effects of the CXCR4 antagonist, AMD3100, in an iodine‑induced autoimmune thyroiditis model were investigated. NOD.H‑2h4 mice were randomly separated into a control, AIT and AIT+AMD3100 groups. The mice were fed with 0.05% sodium iodide water for 8 weeks to induce AIT. The AMD3100‑treated mice were administered with the CXCR4 antagonist at a dose of 10 mg/kg intraperitoneally three times a week during the experimental period. The percentages of CD19+interleukin (IL)10+ B cells and CD4+IL10+ T cells, and the mRNA expression levels of IL10 in the splenocytes were reduced in the AIT group, compared with the control group, however, they increased following AMD3100 treatment, compared with the untreated AIT group. The percentages of CD4+ T cells, CD8+ T cells, CD19+ B cells and CD8+ interferon (IFN)γ+ T cells, and the mRNA expression levels of IFNγ increased in the AIT group, compared with the control group, however, these were reduced in the AMD3100 group, compared with the AIT group. The AMD3100‑treated mice also had lower serum thyroglobulin antibody titers and reduced lymphocytic infiltration in the thyroid, compared with the untreated AIT mice. These results suggested that inhibition of this chemokine axis may offer potential as a therapeutic target for the treatment of AIT.
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Shiqiao
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Chenyan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Jin
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Chenling
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Department of Endocrinology and Metabolism, The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Teng
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001596:Benzylamines; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D000080027:Cyclams; D004797:Enzyme-Linked Immunosorbent Assay; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008856:Microscopy, Fluorescence; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012974:Sodium Iodide / Q000633:toxicity; D013601:T-Lymphocytes / Q000166:cytology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013967:Thyroiditis, Autoimmune / Q000139:chemically induced / Q000473:pathology* / Q000662:veterinary
chemical_list: D000906:Antibodies; D001596:Benzylamines; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D016753:Interleukin-10; D007371:Interferon-gamma; D013954:Thyroglobulin; D012974:Sodium Iodide; C088327:plerixafor