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231223s2009 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2009.05.019
|2 doi
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|a pubmed24n0632.xml
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|a (DE-627)NLM189599111
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|a (NLM)19559654
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|a DE-627
|b ger
|c DE-627
|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Christophi, George P
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a Interferon-beta treatment in multiple sclerosis attenuates inflammatory gene expression through inducible activity of the phosphatase SHP-1
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|c 2009
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| 336 |
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 08.10.2009
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|a Date Revised 20.10.2021
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a 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
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|a Journal Article
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|a Research Support, N.I.H., Extramural
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|a Research Support, Non-U.S. Gov't
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| 650 |
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|a Cytokines
|2 NLM
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| 650 |
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|a NF-kappa B
|2 NLM
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| 650 |
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|a RNA, Small Interfering
|2 NLM
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| 650 |
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|a STAT1 Transcription Factor
|2 NLM
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| 650 |
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|a STAT1 protein, human
|2 NLM
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| 650 |
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7 |
|a STAT6 Transcription Factor
|2 NLM
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| 650 |
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7 |
|a STAT6 protein, human
|2 NLM
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| 650 |
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7 |
|a Interferon-beta
|2 NLM
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| 650 |
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7 |
|a 77238-31-4
|2 NLM
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| 650 |
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|a Protein Tyrosine Phosphatase, Non-Receptor Type 6
|2 NLM
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| 650 |
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7 |
|a EC 3.1.3.48
|2 NLM
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| 650 |
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7 |
|a Interferon beta-1a
|2 NLM
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| 650 |
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7 |
|a XRO4566Q4R
|2 NLM
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| 700 |
1 |
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|a Panos, Michael
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Hudson, Chad A
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Tsikkou, Chriso
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Mihai, Cornelia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Mejico, Luis J
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Jubelt, Burk
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Massa, Paul T
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 133(2009), 1 vom: 17. Okt., Seite 27-44
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
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|g volume:133
|g year:2009
|g number:1
|g day:17
|g month:10
|g pages:27-44
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| 856 |
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|u http://dx.doi.org/10.1016/j.clim.2009.05.019
|3 Volltext
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|a AR
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| 952 |
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|d 133
|j 2009
|e 1
|b 17
|c 10
|h 27-44
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