Methimazole as an antioxidant and immunomodulator in thyroid cells : mechanisms involving interferon-γ signaling and H2O2 scavenging

Cited 40 time in scopus
Metadata Downloads
Title
Methimazole as an antioxidant and immunomodulator in thyroid cells : mechanisms involving interferon-γ signaling and H2O2 scavenging
Author(s)
Ho Kim; Tae Hoon Lee; Young Sun Hwang; Mi Ae Bang; Kang Hwa Kim; Jae Mi Suh; Hyo Kyun Chung; Dae Yeul Yu; Kyung Kwang Lee; O Yu Kwon; Hong Kyu Ro; Min Ho Shong
Bibliographic Citation
Molecular Pharmacology, vol. 60, no. 5, pp. 972-980
Publication Year
2001
Abstract
The antithyroid drug, methimazole (MMI) is used to treat patients with Graves' hyperthyroidism. The major action of MMI is to inhibit synthesis of thyroid hormone in the thyroid gland. However, MMI also has antioxidant and immunomodulatory effects on thyrocytes and/or immune cells. This study identifies novel antioxidant and immunomodulatory effects of MMI involving the interferon-γ (IFN-γ) signaling pathway in thyroid cells. MMI inhibits transcription of the intercellular adhesion molecule-1 (ICAM-1) gene by modulating the function of transcription factor STAT1 (signal transducer and activator of transcription 1), which binds to the IFN-γ activated site of the ICAM-1 promoter. Furthermore, MMI rapidly eliminates H2O2 produced by IFN-γ treatment in thyroid cells and thus inhibits the H2O2-mediated phosphorylation of tyrosine 701 in STAT1. MMI also eliminates H2O2 in vitro. MMI facilitates electron transfer from NADPH to H2O2 using thioredoxin or glutathione, fulfilling a role similar to peroxiredoxin or glutathione peroxidase, respectively. MMI prevents the IFN-γ and H2O2-mediated reversible inactivation of phosphatases. These effects inhibit full activation of the IFN-γ-induced Janus kinase(JAK)/STAT signaling pathway in FRTL-5 thyroid cells. These results may in part explain the antioxidant and immunomodulatory effects of MMI in thyroid cells of Graves' disease patients.
ISSN
0026-895X
Publisher
Amer Soc Pharmacology Experimental Therapeutics
DOI
http://dx.doi.org/10.1124/mol.60.5.972
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.