Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9015970 | Pharmacology & Therapeutics | 2005 | 29 Pages |
Abstract
Phosphodiesterase 4 (PDE4) is a major cyclic AMP-hydrolyzing enzyme in inflammatory and immunomodulatory cells. The wide range of inflammatory mechanisms under control by PDE4 points to this isoenzyme as an attractive target for new anti-inflammatory drugs. Selective inhibitors of PDE4 have demonstrated a broad spectrum of anti-inflammatory activities including the inhibition of cellular trafficking and microvascular leakage, cytokine and chemokine release from inflammatory cells, reactive oxygen species production, and cell adhesion molecule expression in a variety of in vitro and in vivo experimental models. The initially detected side effects, mainly nausea and emesis, appear at least partially overcome by the 'second generation' PDE4 inhibitors, some of which like roflumilast and cilomilast are in the later stages of clinical development for treatment of chronic obstructive pulmonary disease. These new drugs may also offer opportunities for treatment of other inflammatory diseases.
Keywords
VLA-4BALpKaIFN-γPKCGM-CSFLFA-1phorbol 12-myristate 13-acetateVCAM-1NF-κBMIP-1αfMLPMAdCAM-1Th1Th2granulocyte monocyte-colony stimulating factorT helper type 2T helper type 1ICAM-1CREBLPSMCPcGMPPDEHUVECcAMPPMAN-Formyl-Met-Leu-Pheleukocyte function-associated antigen-1inflammationimmunoglobulin interferon-γinterleukinChronic obstructive pulmonary diseaseCOPDtumour necrosis factor-αvery late antigen-4CAMHuman umbilical vein endothelial cellCytokinesPlatelet-activating factorTNF-αnuclear factor-κBPhosphodiesterasebronchoalveolar lavagelipopolysaccharideRANTESPhosphodiesterase 4 inhibitorscell adhesion moleculesmucosal addressin cell adhesion molecule-1Cell adhesion moleculeintercellular cell adhesion molecule-1vascular cell adhesion molecule-1PAFMacrophage inflammatory protein-1αmonocyte chemoattractant proteincAMP-responsive element-binding proteinProtein kinase CprostaglandinChemokines
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Pharmacology
Authors
MarÃa Jesús Sanz, Julio Cortijo, Esteban J. Morcillo,