<p>The Role of Toll-Like Receptors 2 and 4 in the Pathogenesis of Chronic Obstructive Pulmonary Disease</p>

Abstract

Currently, chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. The determination of immune mechanisms of inflammation in the disease presents an important challenge for fundamental medical research. According to modern views, Toll-like receptors (TLRs), among which TLR2 and TLR4 play a key role, are one of the essential components of inflammatory process in COPD. This review focuses on following aspects: the role of TLR2 and TLR4 in the initiation of inflammatory process in COPD; the mechanisms of influence of various exogenous factors (cigarette smoke, suspended particulate matter, and bacteria) on the expression of TLR2 and TLR4; the contribution of these TLRs to the T-helper (Th) immune response development in COPD, in particular to the Th17 immune response, which contributes to the progression of the disease and therapeutic implications of TLR2 and TLR4 in COPD.

Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease

“…Toll-like receptors are known to be implicated in the regulation of cytokine response in adaptive and innate immune cells. According to the results of numerous studies, TLR2 is one of the most important contributors to the pathogenesis of COPD [ 22 – 25 ]. In COPD, ligands for TLR2 can be PAMPs (lipopeptides, glycolipids, lipoteichoic acid (LTA), peptidoglycan (PGN), etc.)…”

“…A number of publications have reported the participation of endosomal TLRs recognizing viruses, such as TLR3, TLR7, and TLR9, in the pathogenesis of COPD [ 15 – 20 ]. However, numerous studies indicate the considerable contribution of membrane TLR2 and TLR4 activated by bacterial PAMPs to the development of the inflammatory process in COPD [ 21 – 25 ]. Altered expression of these TLRs in the tissues of the respiratory tract has been found both in patients with COPD and experimental animals [ 21 , 26 – 29 ].…”

Participation of ABCA1 Transporter in Pathogenesis of Chronic Obstructive Pulmonary Disease

“…Bacterial colonization of the bronchi caused by a defect in phagocytosis in COPD [ 177 ]. Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis and Pseudomonas aeruginosa are most often found in the lower respiratory tract in COPD [ 178 , 179 ]. Bacterial colonization leads to dysregulation of the immune response, also with the participation of TLR4.…”

Lipid-Induced Mechanisms of Metabolic Syndrome

“…TLR4 was the first TLR reported in humans; it is expressed in innate immune cells, including monocytes, macrophages, and dendritic cells, as well as in other cell types, such as adipocytes, enterocytes, and muscle cells. TLR4 is a membrane-associated receptor involved in lipid recognition [ 66 ]. TLRs are activated both by the influence of endogenous ligands and by the participation of lipids—cholesterol, SFAs, and oxidized forms of phospholipids [ 67 ].…”

“…Other mechanisms modulate the inflammatory response by fatty acids based on binding G protein-coupled receptor 120 (GPR120) [ 66 ]. GPR120 is a free fatty acid 4 receptor (FFAR4), and GPR120 activation induced by n-3 PUFA leads to β -arrestin 2 recruitment to the plasma membrane where this protein binds to GPR120 (see Figure 2 ) The GPR120/ β -arrestin 2 complex is internalized into the cytoplasmic compartment where this complex binds to the TAK1-binding protein (TAB1).…”