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

Author(s):

Francesco Nucera, Federica Lo Bello, Sj S. Shen, Paolo Ruggeri, Irene Coppolino, Antonino Di Stefano, Cristiana Stellato, Vincenzo Casolaro, Phil M. Hansbro, Ian M. Adcock and Gaetano Caramori*   Pages 1 - 76 ( 76 )

Abstract:


Chronic obstructive pulmonary disease (COPD) represents a heightened inflammatory response in the lung generally resulting 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 products (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 preclinical development. Inhibition of only a single atypical chemokine or receptor may not block inflammatory processes because 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 antiinflammatory 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 atypical chemokines in COPD pathophysiology and thereby improve COPD management.

Keywords:

Airway inflammation, alveolar macrophages, atypical chemokines, atypical chemokine receptors, chronic obstructive pulmonary disease, lymphocytes, small airways.

Affiliation:

Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina, Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina, Centre for Inflammation, Centenary Institute, Sydney, and Univer-sity of Technology Sydney, Faculty of Science, Ultimo, NSW, Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina, Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina, Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell’Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri, IRCCS, Veruno (NO), Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Salerno, Centre for Inflammation, Centenary Institute, Sydney, and University of Technology Sydney, Faculty of Science, Ultimo, NSW, Airway Disease Section, National Heart and Lung Institute, Imperial College, London, Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Messina



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