Actions of Thyroid Hormone Analogues on Chemokines

被引:34
作者
Davis, Paul J. [1 ,2 ]
Glinsky, Gennadi V. [3 ]
Lin, Hung-Yun [4 ,5 ]
Mousa, Shaker A. [2 ]
机构
[1] Albany Med Coll, Dept Med, Albany, NY 12208 USA
[2] Albany Coll Pharm & Hlth Sci, Pharmaceut Res Inst, Albany, NY 12144 USA
[3] Univ Calif San Diego, Inst Engn Med, San Diego, CA 92093 USA
[4] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Canc Biol & Drug Discovery, Taipei 11031, Taiwan
[5] Taipei Med Univ, Taipei Canc Ctr, Taipei 11031, Taiwan
关键词
CHOROID-PLEXUS; MICROGLIA/MACROPHAGE POLARIZATION; MULTIPLE-SCLEROSIS; NONGENOMIC ACTIONS; WHITE-MATTER; CANCER-CELLS; BRAIN; ACTIVATION; EXPRESSION; RECEPTOR;
D O I
10.1155/2016/3147671
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
The extracellular domain of plasma membrane integrin alpha v beta 3 contains a receptor for thyroid hormone (L-thyroxine, T-4; 3,5,3'-triiodo-L-thyronine, T-3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T-4 and T-3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T-4 and T-3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to alpha v beta 3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance.
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页数:7
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