alexa Cyclic Nucleotide Phosphodiesterase (PDE) Implication In Lupus Erythematosus: Effect Of A New PDE4 Inhibitor | 63452
ISSN: 1745-7580

Immunome Research
Open Access

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

8th Molecular Immunology and Immunogenetics Congress

Claire Lugnier
CNRS, France
Keynote: J Immunome Res
DOI: 10.4172/1745-7580.C1.010
Abstract
Lupus erythematosus is a multigenic inflammatory autoimmune disease that is usually treated with corticoids, anti-TNFα compounds, and anti- CD20, by acting non-selectively, inducing unwanted effects. Cyclic nucleotide phosphodiesterases (PDEs) play a major role in intracellular signaling by hydrolyzing the second messenger cyclic AMP and/or cyclic GMP, according to their subtypes. Since PDE is able to modulate inflammatory processes such as TNFα and other cytokines, one could wonder whether a PDE inhibitor might be beneficial in lupus treatment. Therefore, the evolution of PDE activity and expression levels during the course of the disease in MRL/lpr lupus-prone mice, as well as the biological and the clinical effects of treatments with three different PDE inhibitors: pentoxifylline (100μg), denbufylline (100μg) and NCS 613 (30μg) was evaluated in these mice. The comparison of kidney PDE4 activity progression of MRL/lpr mice with CBA/J control mice reveals an increase of activity with the disease progression, whereas PDE2 and PDE3 activities are not significantly changed. When treated with PDE inhibitors, the most potent and selective PDE4 inhibitor NCS 613 (IC50=42 nM) was also found to be the most effective molecule in decreasing proteinuria and increasing survival rate of MRL/lpr mice. NCS 613 is a potent inhibitor which is more selective for PDE4C subtype (IC50: 1.4 nM) and has an affinity for the high affinity rolipram binding site (HARBS) and relatively low (Ki=148 nM) in comparison to rolipram (Ki=3 nM) suggesting few emetic effect. Interestingly, NCS 613 inhibits basal and LPS-induced TNFa secretion from PBLs of lupus patients, as well as from MRL/lpr peripheral blood lymphocytes (PBLs), pointing out the therapeutic potential of NCS 613 in systemic lupus. This study reveals that PDE4 represent a potential therapeutic target in lupus disease and that the original compound NCS 613 delay lupus disease progression.
Biography

Claire Lugnier has experience in studying the role of cyclic nucleotide phosphodiesterases (PDE) in normal and pathophysiological signaling and conceiving specific and selective PDE inhibitors. She has based her knowledge mainly on PDE1-PDE5 after years of experience in research and teaching.

Email: [email protected]

image PDF   |   image HTML
 

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7