CXCR4 antagonist AMD3100 ameliorates thyroid damage in autoimmune thyroiditis in NOD.H‑2h⁴ mice.
CXCR4 antagonist AMD3100 ameliorates thyroid damage in autoimmune thyroiditis in NOD.H‑2h⁴ mice.
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DOI：
10.3892/mmr.2016.4965
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发表时间：
2016-04
影响因子：
3.4
通讯作者：
Xin Liu;J. Mao;Cheng Han;Shiqiao Peng;Chen-yan Li;Ting Jin;C. Fan;Z. Shan;W. Teng
中科院分区：
文献类型：
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作者：
Xin Liu;J. Mao;Cheng Han;Shiqiao Peng;Chen-yan Li;Ting Jin;C. Fan;Z. Shan;W. Teng
CXC趋化因子配体12（CXCL 12）及其受体CXC趋化因子受体4（CXCR 4）在患有自身免疫性甲状腺疾病的小鼠中上调。然而，这种相互作用是否涉及自身免疫性甲状腺炎（AIT）的病理生理学仍有待阐明。在本研究中，研究了CXCR 4拮抗剂AMD 3100在碘诱导的自身免疫性甲状腺炎模型中的作用。NOD.H-2 h4小鼠随机分为对照组、AIT组和AIT+ AMD 3100组。用0.05%碘化钠水喂养小鼠8周以诱导AIT。在实验期间，以10 mg/kg的剂量每周三次腹腔注射给予AMD 3100处理小鼠CXCR 4拮抗剂。与对照组相比，AIT组脾细胞中CD 19 + IL 10+ B细胞和CD 4 + IL 10 + T细胞的百分比以及IL 10的mRNA表达水平降低，但与未治疗的AIT组相比，AIT组的CD 19 + IL 10+ B细胞和CD 4 + IL 10 + T细胞的百分比以及IL 10的mRNA表达水平升高。与对照组相比，AIT组CD 4 + T细胞、CD 8 + T细胞、CD 19 + B细胞和CD 8 + IFN γ+ T细胞的百分比以及IFNγ mRNA的表达水平均升高，而AMD 3100组则降低。与未处理的AIT小鼠相比，AMD 3100处理的小鼠的血清甲状腺球蛋白抗体滴度也较低，甲状腺中的淋巴细胞浸润减少。这些结果表明，该趋化因子轴的抑制可能提供作为治疗AIT的治疗靶点的潜力。
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.