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Pharmacological Inhibition of cAMP Signaling is an Attractive Therapeutic Strategy for Management of Chronic Inflammatory and Autoimmune Diseases | Abstract
Journal of Clinical and Cellular Immunology

Journal of Clinical and Cellular Immunology
Open Access

ISSN: 2155-9899

+44 2038689735

Abstract

Pharmacological Inhibition of cAMP Signaling is an Attractive Therapeutic Strategy for Management of Chronic Inflammatory and Autoimmune Diseases

Issaka Yougbare

Systemic Lupus Erythematosus (SLE) evolves into progressive and chronic inflammation of multiple joints and organs. No specific treatment exists for SLE which presents a diverse clinical polymorphism with unclear pathogenicity. Women at their pre-menopausal age are the most affected and early studies have reported the implication of estrogen in T cell abnormalities. Alteration of cAMP signaling in immune cells and target organs is emerging as cellular mechanism governing SLE disease progression. We recently reported that activity and expressions of PDE4, the major cAMP hydrolyzing enzyme were deregulated in kidney of lupus prone mice. Therefore, PDE4 inhibitors may exert anti-inflammatory effects on several immunocompetent cells including T and B lymphocytes, and macrophages. Several PDE4 inhibitors achieved good therapeutic values as potent anti-inflammatory compounds for the treatment of chronic inflammatory diseases including Crohn's disease, autoimmune disease (lupus), COPD, and neurodegenerative diseases. This review will discuss the mechanism of NCS 613, a new cAMP elevating agent in preventing systemic chronic inflammation in SLE. This PDE4 inhibitor is believed to reduce abnormal systemic inflammation orchestrated by overreactive T cells that stimulate autoantibodies production by autoreactive B cells and proinflammatory mediators release by macrophages. Ultimately, NCS 613 improve survival and overcome nephritis in mice and prevent inflammatory cytokines release in human stimulated leucocytes. PDE4 inhibition is a promising therapeutic target to tackle chronic inflammatory disease of different pathogenicity.

Published Date: 2021-02-26; Received Date: 2021-02-05

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