Role of Atypical Chemokines and Chemokine Receptors Pathways in the Pathogenesis of COPD

Abstract

: Chronic obstructive pulmonary disease (COPD) represents a heightened inflammatory response in the lung resulting generally from tobacco smoking-induced recruitment and activation of inflammatory cells and/or activation of lower airway structural cells. Several mediators can modulate activation and recruitment of these cells, particularly those belonging to the chemokines (conventional and atypical) family. There is emerging evidence for complex roles of atypical chemokines and their receptors [such as high mobility group box 1 (HMGB1), antimicrobial peptides, receptor for advanced glycosylation end product (RAGE) or toll-like receptors (TLRs)] in the pathogenesis of COPD, both in the stable disease and during exacerbations. Modulators of these pathways represent potential novel therapies for COPD and many are now in pre-clinical development. Inhibition of only a single atypical chemokine or receptor may not block inflammatory processes, be-cause there is redundancy in this network. However, there are many animal studies that encourage studies for modulating the atypical chemokine network in COPD. Thus, few pharmaceutical companies maintain a significant interest in developing agents that target these molecules as potential anti-inflammatory drugs. Antibody-based (biological) and small molecule drug (SMD)-based therapies targeting atypical chemokines and/or their receptors are mostly at the preclinical stage and their progression to clinical trials is eagerly awaited. These agents will most likely enhance our knowledge about the role of a typical chemokines in COPD pathophysiology and thereby improve COPD management.

An Overview of the Safety and Efficacy of Monoclonal Antibodies for the Chronic Obstructive Pulmonary Disease

“…The redundancy of signal-induced effects, particularly the possibility that other pathways can still induce or maintain the inflammatory state even when a specific pathway is turned off, represents a high critical point that must always be considered when evaluating the effects of mAbs in COPD. 83 It is the most likely cause of failure when blocking a single specific pathway and is, furthermore, a major obstacle to the development of targeted therapies. 6…”

Cellular and molecular features of COVID-19 associated ARDS: therapeutic relevance

“…Levels of the soluble receptor for advanced glycation end products (sRAGE) in serum are increased in several inflammatory disease associated to lung epithelial injury, such as bacterial infection, COPD, lung fibrosis and “classical” ARDS [ 126 , 144 ]. However, there is limited data on the role of sRAGE in c-ARDS.…”

The role of HMGB1/RAGE/TLR4 signaling pathways in cigarette smoke‐induced inflammation in chronic obstructive pulmonary disease

“…Upregulation of HMGB1, RAGE, and TLR4 protein levels were detected in lung tissue of COPD smoker, bronchoalveolar lavage fluid (BALF), serum and other samples. However, inhibiting the expression of this pathway or its components can alleviate the degree of inflammation 23–26 . Herein, we discuss the role of HMGB1, RAGE, and TLR4 in the cigarette smoke‐induced inflammatory response in COPD.…”

“…However, inhibiting the expression of this pathway or its components can alleviate the degree of inflammation. [23][24][25][26] Herein, we discuss the role of HMGB1, RAGE, and TLR4 in the cigarette smoke-induced inflammatory response in COPD.…”