SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients.

Laboratory Investigation; a Journal of Technical Methods and Pathology
George P ChristophiPaul T Massa

Abstract

Recent studies in mice have demonstrated that the protein tyrosine phosphatase SHP-1 is a crucial negative regulator of cytokine signaling, inflammatory gene expression, and demyelination in central nervous system. The present study investigates a possible similar role for SHP-1 in the human disease multiple sclerosis (MS). The levels of SHP-1 protein and mRNA in PBMCs of MS patients were significantly lower compared to normal subjects. Moreover, promoter II transcripts, expressed from one of two known promoters, were selectively deficient in MS patients. To examine functional consequences of the lower SHP-1 in PBMCs of MS patients, we measured the intracellular levels of phosphorylated STAT6 (pSTAT6). As expected, MS patients had significantly higher levels of pSTAT6. Accordingly, siRNA to SHP-1 effectively increased the levels of pSTAT6 in PBMCs of controls to levels equal to MS patients. Additionally, transduction of PBMCs with a lentiviral vector expressing SHP-1 lowered pSTAT6 levels. Finally, multiple STAT6-responsive inflammatory genes were increased in PBMCs of MS patients relative to PBMCs of normal subjects. Thus, PBMCs of MS patients display a stable deficiency of SHP-1 expression, heightened STAT6 phosphorylation, a...Continue Reading

References

Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A de BustrosS B Baylin
Aug 4, 1995·The Journal of Biological Chemistry·A YetterL C Platanias
Jan 27, 1995·The Journal of Biological Chemistry·J RouleauM Szyf
Nov 5, 1993·Journal of Immunological Methods·L ChangS L Nehlsen-Cannarella
Jun 1, 1997·Current Opinion in Immunology·J C Unkeless, J Jin
Oct 23, 1997·The Journal of Experimental Medicine·W E SuenN H Ruddle
Jun 24, 1998·Cellular Immunology·A R KhaledJ Schiffenbauer
Aug 26, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·P T Massa, C Wu
Dec 16, 1998·The Journal of Biological Chemistry·S J HaqueB R Williams
Mar 17, 1999·The Journal of Clinical Investigation·T L SørensenR M Ransohoff
Dec 10, 1999·The Journal of Experimental Medicine·A HmadchaE Pintado
Sep 28, 2000·The New England Journal of Medicine·J H NoseworthyB G Weinshenker
Oct 29, 2000·The Journal of Biological Chemistry·J J MüllerU Heinemann
Nov 18, 2000·AIDS Research and Human Retroviruses·S WrzesinskiG Feuer
Jun 21, 2001·American Journal of Respiratory Cell and Molecular Biology·S MatsukuraR P Schleimer
Jun 20, 2002·European Journal of Biochemistry·Hing Wo TsuiFlorence Wing Ling Tsui
Jul 24, 2002·FEBS Letters·Augustin AmourGillian Murphy
Aug 7, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Andrea SalmaggiMarco De Rossi
Dec 4, 2002·Japanese Journal of Cancer Research : Gann·Toshiya OsawaMasashi Fukayama
Jan 4, 2003·The Journal of Clinical Investigation·Tohru KamataToshinori Nakayama

❮ Previous
Next ❯

Citations

Apr 3, 2012·Inflammatory Bowel Diseases·George P ChristophiSteve K Landas
Nov 12, 2009·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joseph J SabatinoBrian D Evavold
Jan 16, 2010·Immunologic Research·Zhou ZhuTao Zheng
May 28, 2013·Nature·John R LukensThirumala-Devi Kanneganti
Jun 17, 2008·Journal of Leukocyte Biology·Chad A HudsonPaul T Massa
Dec 15, 2010·PloS One·Carlos RiverosUNKNOWN ANZgene Multiple Sclerosis Genetics Consortium
Jul 24, 2014·Rare Diseases·John R Lukens, Thirumala-Devi Kanneganti
Dec 17, 2017·Immunological Reviews·Ankit Malik, Thirumala-Devi Kanneganti
Apr 29, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·George P ChristophiPaul T Massa
Aug 8, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sarang TarteyThirumala-Devi Kanneganti
Jan 7, 2010·Basic & Clinical Pharmacology & Toxicology·Raymond F GenoveseAshima Saxena
Apr 25, 2012·Cellular and Molecular Life Sciences : CMLS·Kristina LudigsGreta Guarda
Mar 22, 2014·Neuromolecular Medicine·Cem Ismail KüçükaliErdem Tüzün
Dec 17, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ben A CrokerAndrew W Roberts
Mar 1, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ying WangMonica Kraft
Jan 21, 2017·Biomolecular Concepts·Fereshteh AlsahebfosoulShamsi Naderi
Mar 12, 2008·Journal of Neurochemistry·George P ChristophiPaul T Massa
Apr 27, 2017·Journal of Molecular Neuroscience : MN·Marta WagnerMonika Jasek
May 12, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·S Elizabeth FranksJohn C Cambier
Apr 24, 2018·Frontiers in Immunology·S Elizabeth Franks, John C Cambier
May 30, 2019·Frontiers in Immunology·Angelo V MarzanoMassimo Cugno
Mar 24, 2020·Cellular & Molecular Immunology·Sarang TarteyThirumala-Devi Kanneganti
Apr 10, 2018·The Journal of Clinical Investigation·Sarang TarteyThirumala-Devi Kanneganti
May 24, 2017·Scientific Reports·Anupam AdhikariMartin Olivier
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Patricia Castro-SanchezRose Zamoyska

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.