alexa Differential activation of JAK enzymes in rheumatoid arthritis and autoimmune disorders by proinflammatory cytokines – potential drug targets.
Immunology

Immunology

Immunotherapy: Open Access

Author(s): Charles Malemud

Abstract Share this page

Although several pro-inflammatory cytokines including interleukin-6 (IL-6), IL-7, IL-12/IL-23, IL-17, IL-2, interferon, and the anti-inflammatory cytokines, IL-4/IL-13, IL-10, and IL-22, all activate the Janus kinase/signal transducers and activators of transcription (JAK/ STAT) pathway, in autoimmune disorders, a skewing of the cytokine repertoire in favor of pro-inflammatory cytokines results in amplifying the effects of pro-inflammatory cytokines. An apparent deficiency of anti-inflammatory cytokines to counterbalance the 'ramping up' of pro-inflammatory cytokine-mediated activation of JAK/STAT is also significant, while endog-enous negative regulators of cytokine signaling and JAK/STAT activation may also be com-promised. In addition, JAK/STAT pathway activation can result in activation of stress-activated protein/mitogen-activated protein kinase (SAP/MAPK) and phosphatidylinositol-3-kinase/ Akt/ mammalian target of rapamycin pathways that are instrumental in promoting matrix metal-loproteinase gene expression, aberrant cell survival, and osteoclast differentiation. The critical role played by pro-inflammatory cytokines in differentially activating JAK/STAT and parallel signal transduction pathways resulted in the development of several cytokine/cytokine receptor neutralizing monoclonal antibodies and fusion proteins that are currently employed for treating rheumatoid arthritis, Crohn's disease, and psoriasis. Small molecule inhibitors (SMIs) that target specific JAK enzymes have led to the development of CP690550, a JAK3-specific SMI, which is the first JAK-specific SMI to reach phase III in a rheumatoid arthritis clinical trial. This article was published in Int J Interferon Cytokine Mediator Res and referenced in Immunotherapy: Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

agrifoodaquavet@omicsonline.com

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

clinical_biochem@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

chemicaleng_chemistry@omicsonline.com

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

environmentalsci@omicsonline.com

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

engineering@omicsonline.com

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

generalsci_healthcare@omicsonline.com

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

genetics_molbio@omicsonline.com

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immuno_microbio@omicsonline.com

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

omics@omicsonline.com

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

mathematics_physics@omicsonline.com

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

medical@omicsonline.com

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuro_psychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

pharma@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords