More MS news articles for Nov 2001

Interferon-beta therapy downregulates the anti-apoptosis protein FLIP in T cells from patients with multiple sclerosis

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11694335&dopt=Abstract

J Neuroimmunol 2001 Jan 11;120(1-2):199-207
Sharief MK, Semra YK, Seidi OA, Zoukos Y.
Department of Neuroimmunology, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, Hodgkin Building, SE1 9RT, London, UK

Interferon-beta reduces clinical exacerbations in multiple sclerosis (MS) through several immunomodulatory mechanisms that may involve augmentation of programmed cell death (apoptosis) of T lymphocytes.

The anti-apoptosis protein FLIP (Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein) has been recently identified as a potent regulator of T lymphocyte susceptibility to apoptosis.

In a prospective study, we evaluated the expression of FLIP and other apoptosis regulatory proteins in ex vivo activated T lymphocytes from MS patients, before and serially after treatment with interferon-beta.

We also investigated the long-term effects of interferon-beta on T cell apoptosis in a cross-sectional study of MS patients receiving chronic drug therapy.

Treatment with interferon-beta reduced the expression of FLIP isoforms in activated T lymphocytes.

This reduced expression correlated with augmented T cell susceptibility to apoptosis and with clinical response to treatment.

In contrast, interferon-beta therapy did not alter cellular expression of the anti-apoptotic protein Bcl-2.

This downregulatory effect of interferon-beta on cellular FLIP expression was maintained following long-term therapy.

Our findings suggest that interferon-beta therapy exerts a regulatory effect on peripheral T lymphocytes through a pro-apoptosis mechanism that involves the downregulation of cellular FLIP expression.
 

PMID: 11694335 [PubMed - in process]