Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Clin Immunol ; 133(1): 27-44, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19559654

ABSTRACT

Interferon-beta is a current treatment for multiple sclerosis (MS). Interferon-beta is thought to exert its therapeutic effects on MS by down-modulating the immune response by multiple potential pathways. Here, we document that treatment of MS patients with interferon beta-1a (Rebif) results in a significant increase in the levels and function of the protein tyrosine phosphatase SHP-1 in PBMCs. SHP-1 is a crucial negative regulator of cytokine signaling, inflammatory gene expression, and CNS demyelination as evidenced in mice deficient in SHP-1. In order to examine the functional significance of SHP-1 induction in MS PBMCs, we analyzed the activity of proinflammatory signaling molecules STAT1, STAT6, and NF-kappaB, which are known SHP-1 targets. Interferon-beta treatment in vivo resulted in decreased NF-kappaB and STAT6 activation and increased STAT1 activation. Further analysis in vitro showed that cultured PBMCs of MS patients and normal subjects had a significant SHP-1 induction following interferon-beta treatment that correlated with decreased NF-kappaB and STAT6 activation. Most importantly, experimental depletion of SHP-1 in cultured PBMCs abolished the anti-inflammatory effects of interferon-beta treatment, indicating that SHP-1 is a predominant mediator of interferon-beta activity. In conclusion, interferon-beta treatment upregulates SHP-1 expression resulting in decreased transcription factor activation and inflammatory gene expression important in MS pathogenesis.


Subject(s)
Interferon-beta/therapeutic use , Multiple Sclerosis/drug therapy , NF-kappa B/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism , STAT1 Transcription Factor/metabolism , STAT6 Transcription Factor/metabolism , Adult , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Cells, Cultured , Cytokines/blood , Female , Gene Silencing/immunology , Humans , Interferon beta-1a , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Male , Middle Aged , Multiple Sclerosis/immunology , NF-kappa B/antagonists & inhibitors , NF-kappa B/immunology , Protein Tyrosine Phosphatase, Non-Receptor Type 6/drug effects , Protein Tyrosine Phosphatase, Non-Receptor Type 6/genetics , Protein Tyrosine Phosphatase, Non-Receptor Type 6/immunology , RNA, Small Interfering/immunology , RNA, Small Interfering/metabolism , STAT1 Transcription Factor/agonists , STAT1 Transcription Factor/immunology , STAT6 Transcription Factor/antagonists & inhibitors , STAT6 Transcription Factor/immunology , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...