Actions of Thyroid Hormone Analogues on Chemokines

The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine...

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Main Authors: Paul J. Davis, Gennadi V. Glinsky, Hung-Yun Lin, Shaker A. Mousa
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/3147671
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author Paul J. Davis
Gennadi V. Glinsky
Hung-Yun Lin
Shaker A. Mousa
author_facet Paul J. Davis
Gennadi V. Glinsky
Hung-Yun Lin
Shaker A. Mousa
author_sort Paul J. Davis
collection DOAJ
description The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 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 T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 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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spelling doaj-art-c37ca942c0c040d6bf7ea339725d72d72025-08-20T03:23:11ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/31476713147671Actions of Thyroid Hormone Analogues on ChemokinesPaul J. Davis0Gennadi V. Glinsky1Hung-Yun Lin2Shaker A. Mousa3Department of Medicine, Albany Medical College, Albany, NY 12208, USAInstitute of Engineering in Medicine, University of California, San Diego, CA 92093, USAPhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanPharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY 12144, USAThe extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 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 T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 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.http://dx.doi.org/10.1155/2016/3147671
spellingShingle Paul J. Davis
Gennadi V. Glinsky
Hung-Yun Lin
Shaker A. Mousa
Actions of Thyroid Hormone Analogues on Chemokines
Journal of Immunology Research
title Actions of Thyroid Hormone Analogues on Chemokines
title_full Actions of Thyroid Hormone Analogues on Chemokines
title_fullStr Actions of Thyroid Hormone Analogues on Chemokines
title_full_unstemmed Actions of Thyroid Hormone Analogues on Chemokines
title_short Actions of Thyroid Hormone Analogues on Chemokines
title_sort actions of thyroid hormone analogues on chemokines
url http://dx.doi.org/10.1155/2016/3147671
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