Samah M Elaidy
Suez Canal University, Egypt
Title: Title: Serotonin Receptor Subtype-2 and Idiopathic Pulmonary Fibrosis
Biography
Biography: Samah M Elaidy
Abstract
Augmentation of lung serotonin (5-hydroxytryptamine, 5-HT) content is evident during development of pulmonary fibrosis with the implication of highly expressed metabotropic 5-HT2 receptors in the pathogenesis, ending in various mitogenic and profibrotic effects. In the fibrotic lung microenvironment, three 5-HT2 receptors subtypes- A, B, C- are recognized. The 5-HT2A and 5-HT2B receptors are chiefly confined to fibroblasts, alveolar epithelial cells, with an augmented allocation of 5-HT2C receptors into alveolar macrophages. These unique allocations allow multiple intersecting serotonergic pathways, which modulate different fibro-proliferative and angiogenic key regulators in fibrotic lung microenvironment. Recently in lung fibrosis, 5-HT2C has been found to play a major phenotypical alternating role on alveolar macrophage with subsequent progression into inflammatory-fibrotic cascades. In several recent studies, selective specified pharmacological antagonism of 5-HT2A and/or 2B and/or 2C receptors was found to attenuate bleomycin-induced lung injury and fibrosis through improving lung functions, decreasing lung edema and downregulating several collagen deposition mediators, as tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), connective tissue growth factors (CTGF), plasminogen activator inhibitor-1 (PAI-1), monocyte chemoattractant protein-1 (MAP-1) and vascular endothelial growth factor (VEGF). In conclusion, blockade of 5-HT2A, 2B, and 2C receptors is considered a promising molecular target for pharmacological intervention in fibro-proliferative interstitial lung diseases. However, further studies are needed to explore in depth the complexity of roles played by different 5-HT2 receptor subtypes and the therapeutic implications of antagonizing their effects in idiopathic pulmonary fibrosis.
Keywords: 5-HT2A; 5-HT2B; 5-HT2C; Bleomycin; Cyproheptadine; Idiopathic pulmonary fibrosis; Mirtazapine; RS-102221; Serotonin; Terguride.