Unknown

Dataset Information

0

2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation.


ABSTRACT: The endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatment of lymphocytes specifically reduced the nuclear translocation and transcriptional activity of nuclear factor of activated T-cells (NFAT) c1, whereas NF-?B and activator protein 1 (AP-1) activation were not adversely affected. We therefore propose that 2ME2 attenuates EAE through disruption of the NFAT pathway and subsequent lymphocyte activation. By extension, our findings provide a molecular rationale for the use of 2ME2 as a tolerable oral immunomodulatory agent for the treatment of autoimmune disorders such as MS in humans.

SUBMITTER: Duncan GS 

PROVIDER: S-EPMC3529073 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

2-Methoxyestradiol inhibits experimental autoimmune encephalomyelitis through suppression of immune cell activation.

Duncan Gordon S GS   Brenner Dirk D   Tusche Michael W MW   Brüstle Anne A   Knobbe Christiane B CB   Elia Andrew J AJ   Mock Thomas T   Bray Mark R MR   Krammer Peter H PH   Mak Tak W TW  

Proceedings of the National Academy of Sciences of the United States of America 20121203 51


The endogenous metabolite of estradiol, 2-Methoxyestradiol (2ME2), is an antimitotic and antiangiogenic cancer drug candidate that also exhibits disease-modifying activity in animal models of rheumatoid arthritis (RA). We found that 2ME2 dramatically suppresses development of mouse experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). 2ME2 inhibits in vitro lymphocyte activation, cytokine production, and proliferation in a dose-dependent fashion. 2ME2 treatm  ...[more]

Similar Datasets

| S-EPMC5786528 | biostudies-literature
| S-EPMC8564550 | biostudies-literature
| S-EPMC7547849 | biostudies-literature
| S-EPMC6490025 | biostudies-literature
| S-EPMC7990911 | biostudies-literature
| S-EPMC10798281 | biostudies-literature
| S-EPMC8452861 | biostudies-literature
| S-EPMC5071574 | biostudies-literature
| S-EPMC2684188 | biostudies-literature