Lymphocyte Kv1.3-channels in the pathogenesis of chronic obstructive pulmonary disease: novel therapeutic implications of targeting the channels by commonly used drugsReportar como inadecuado




Lymphocyte Kv1.3-channels in the pathogenesis of chronic obstructive pulmonary disease: novel therapeutic implications of targeting the channels by commonly used drugs - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Allergy, Asthma and Clinical Immunology

, 12:60

First Online: 29 November 2016Received: 11 July 2016Accepted: 15 November 2016

Abstract

In patients with chronic obstructive pulmonary disease COPD, over-activated T-lymphocytes produce pro-inflammatory cytokines and proliferate in situ in the lower airways and pulmonary parenchyma, contributing substantially to the pathogenesis of the disease. Despite our understanding of the molecular mechanisms by which lymphocytes are activated, we know little about the physiological mechanisms. T-lymphocytes predominantly express delayed rectifier K-channels Kv1.3 in their plasma membranes and these channels play crucial roles in inducing the lymphocyte activation and proliferation. In the pathogenesis of chronic inflammatory diseases, such as chronic kidney disease CKD or inflammatory bowel disease IBD, these channels, which are overexpressed in proliferating lymphocytes within the inflamed organs, are responsible for the progression of the diseases. Since the over-activation of cellular immunity is also mainly involved in the pathogenesis of COPD, this disease could share similar pathophysiological features as those of CKD or IBD. From a literature review including ours, it is highly likely that the Kv1.3-channels are overexpressed or over-activated in T-lymphocytes isolated from patients with COPD, and that the overexpression of the channels would contribute to the development or progression of COPD. The involvement of the channels leads to novel therapeutic implications of potentially useful Kv1.3-channel inhibitors, such as calcium channel blockers, macrolide antibiotics, HMG-CoA reductase inhibitors and nonsteroidal anti-inflammatory drugs, in the treatment of COPD.

KeywordsChronic obstructive pulmonary disease COPD Over-activated T-lymphocytes Delayed rectifier K-channels Kv1.3 Therapeutic implications for COPD Kv1.3-channel inhibitor  Download fulltext PDF



Autor: Itsuro Kazama - Tsutomu Tamada

Fuente: https://link.springer.com/article/10.1186/s13223-016-0168-3







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