Expression and polymorphism of lTLR4 receptors in pathogenesis of chronic obstructive pulmonary disease: a modern view

Abstract

Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by irreversible or partially reversible obstruction of the bronchial tree. Currently, there are many proven links in the COPD etiopathogenesis, among which a pivotal role is assigned to the value of the hyperergic inflammatory reaction in response to inhalation of various harmful substances (tobacco smoke, industrial pollutants, etc.). The number of macrophages, neutrophils, lymphocytes increases in the lungs of COPD patients, and these cells secrete a fairly wide range of inflammatory mediators. Bacterial colonization of the airways is one of the key features in COPD pathogenesis leading to persistent or chronic stimulation of immune cells through Tolllike receptors (TLR), which perceive the pathogen-associated molecular patterns (PAMPs).This article provides a review of literature concerning modern concepts of the role of Toll-like receptors expression and polymorphism, in particular, TLR4, in pathogenesis of COPD. TLR4 is a member of the Tolllike receptor family that plays a fundamental role in pathogen identification and innate immune activation. By recognizing the pathogen-associated molecular patterns (PAMPs) expressed on infectious agents, TLRs mediate the production of cytokines necessary for the development of effective immunity. Different TLRs exhibit distinct expression patterns. This receptor is most abundantly expressed in placenta and in the myelomonocytic leukocyte subpopulations. E.g., Di Stefano A. et al. (2017), determined immunohistochemically the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, Toll-interleukin-1-receptor domain containing adapter protein (TIRAP) and interleukin-1-receptor-associated phosphokinases (IRAK1 and IRAK4) in bronchial mucosa of patients with stable COPD of varying severity. It was found that TLR4 expression of the bronchial epithelium positively correlated with degree of obstruction and CD4+ and CD8+T cell contents. Stimulation of TLR4 increases cytokine production, which may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients. The degree of TLR4 involvement into COPD pathogenesis requires more detailed study in future, in order to determine the main mechanisms for emerging inflammatory response in the airways. This review article is part of a research grant project to study pro-inflammatory response to endotoxin of Gram-negative flora in COPD pathogenesis (State registration number – АААА-А19-119122390040-2).