Journal
STEROIDS
Volume 77, Issue 10, Pages 988-995Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.steroids.2012.02.018
Keywords
Nongenomic effect; Integrin alpha v beta 3; RGD; Tetrac; Cell migration; Reactive oxygen species
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It is now widely accepted that thyroid hormones, L-thyroxine (T-4) and 3,3',5-triiodo-L-thyronine (T-3), act as modulators of the immune response. Immune functions such as chemotaxis, phagocytosis, generation of reactive oxygen species, and cytokine synthesis and release, are altered in hypo- and hyper-thyroid conditions, even though for many immune cells no clear correlation has been found between altered levels of T-3 or T-4 and effects on the immune responses. Integrins are extracellular matrix proteins that are important modulators of many cellular responses, and the integrin alpha v beta 3 has been identified as a cell surface receptor for thyroid hormones. Rapid signaling via this plasma membrane binding site appears to be responsible for many nongenomic effects of thyroid hormones, independent of the classic nuclear receptors. Through the integrin alpha v beta 3 receptor the hormone can activate both the ERK1/2 and phosphatidylinositol 3-kinase pathways, with downstream effects including intracellular protein trafficking, angiogenesis and tumor cell proliferation. It has recently become clear that an important downstream target of the thyroid hormone nongenomic pathway may be the mammalian target of rapamycin, mTOR New results demonstrate the capability of T-3 or T-4 to induce in the short time range important responses related to the immune function, such as reactive oxygen species production and cell migration in THP-1 monocytes. Thus thyroid hormones seem to be able to modulate the immune system by a combination of rapid nongenomic responses interacting with the classical nuclear response. (c) 2012 Elsevier Inc. All rights reserved.
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