About this Research Topic
cAMP is involved in many cellular functions and a well-established regulator of immune responses and inflammation. Leukocytes play a critical role in inflammation and its modulation. Function and regulation of different subpopulations of T cells, B cells and NK cells, as well as myeloid cells, such as neutrophils, monocytes, macrophages, and dendritic cells involve activation of the cAMP pathway. Additionally, interactions between leukocytes and endothelial cells are critical during inflammatory lesion formation and can be regulated by cAMP signalling. cAMP is degraded by cyclic nucleotide phosphodiesterase (PDE) enzymes. PDEs are the only enzymes known to hydrolyze cAMP and thereby maintain spatial and temporal control over pools of cAMP within distinct cellular compartments.
PDEs are divided into 11 different gene families based on their specificity for cAMP or cGMP, structural similarity and mode of regulation. While PDEs have been recognized early as potential drug targets for anti-inflammatory drugs, bringing specific PDE inhibitors into clinical use has faced decades of challenges, mostly due to dose-limiting side effects. Major progress has been made with the approval and clinical use of select PDE4 inhibitors to treat major human inflammatory diseases. PDE4-selective inhibitors are used for oral treatment of chronic obstructive pulmonary disease, psoriatic arthritis and plaque psoriasis as well as a topical treatment for atopic dermatitis. Due to the unique roles of specific PDE isoforms to control distinct pools of PDEs in leukocytes, additional PDEs became a focus to study potentially novel therapeutics for inflammation.
This Research Topic aims to showcase recent investigations of PDE functions in inflammation to provide an overview of their potential as targets for the treatment of inflammatory disorders.
We particularly welcome Original Research, Methods and Review articles falling under the following topics:
• Molecular mechanisms of PDE function in leukocytes and endothelial cells
• Drugs (inhibitors, signalling disruptors) targeting PDEs
• Selective functions of distinct PDE isoforms in inflammation
• State-of-the-art of the development of isoform selective PDE inhibitors
Keywords: Endothelial PDEs, Leukocyte PDEs, Inflammation, Autoimmunity, Small molecule PDE inhibitors, Disruptors of cAMP/cGMP signalling, Activators of cAMP/cGMP signalling, Anti-inflammatory therapy
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