Kinase inhibitors in the treatment of obstructive pulmonary diseases

Abstract

Chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD) and asthma, are major causes of death and reduced quality of life. Characteristic of chronic pulmonary disease is excessive lung inflammation that occurs in response to exposure to inhaled irritants, chemicals, and allergens. Chronic inflammation leads to remodeling of the airways that includes excess mucus secretion, proliferation of smooth muscle cells, increased deposition of extracellular matrix proteins and fibrosis. Protein kinases have been implicated in mediating inflammatory signals and airway remodeling associated with reduced lung function in chronic pulmonary disease. This review will highlight the role of protein kinases in the lung during chronic inflammation and examine opportunities to use protein kinase inhibitors for the treatment of chronic pulmonary diseases.

An epigenome-wide study of DNA methylation profiles and lung function among American Indians in the Strong Heart Study

“…Protein kinases play a role in many key pulmonary cellular responses, including mediating inflammatory signals and airway remodeling. Thus, they have been proposed as therapeutic targets for several lung diseases such as chronic obstructive pulmonary disease and asthma [37,38]. PIM1 and CKD5, top genes associated with FEV1 and FVC, respectively, are serine/threonine protein kinases.…”

Constitutive immune activity promotes JNK- and FoxO-dependent remodeling of Drosophila airways

“…A certain level of JNK/FoxO activation/deregulation caused by chronic input can remain inconspicuous over a long time, but an additional stressor, such as an infection, might cause activation above the threshold, leading to remodeling of the airways (Broide, 2008;Cheng et al, 2007;Hart et al, 1998;Holgate, 2007b). Taking into account this highly important role of the JNK/FoxO axis for disease-associated remodeling processes, utilizing these signaling systems as intervention targets in chronic lung diseases is an emerging but highly promising field (Al-Tamari et al, 2018;Defnet et al, 2020;Eurlings et al, 2017;van der Velden et al, 2016).…”

Novel Immunomodulatory Therapies for Respiratory Pathologies

“…Activation of protein kinases has been implicated in the transduction of signals triggered by inflammatory mediators. Several kinases were shown to be overactivated in COPD, thus promoting hyper-contractility of airways, mucus hypersecretion, immune cell infiltration, and airway remodeling ( Defnet et al, 2020 ; Barnes, 2016 ; Pirozzi et al, 2019 ). Kinase inhibitors, mostly developed for cancer treatment, might be particularly interesting in the context of COPD to cease the inflammatory process.…”