S100A8/A9 as a Pro-inflammatory Cytokine in Obstructive Airway Disease Via the Multi-Ligand Receptor, RAGE

ISSN: 1875-614X (Online)
ISSN: 1871-5230 (Print)


Volume 15, 3 Issues, 2016


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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents

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Editor-in-Chief:
Claudiu T. Supuran
Neurofarba Department
University of Florence
Florence
Italy


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S100A8/A9 as a Pro-inflammatory Cytokine in Obstructive Airway Disease Via the Multi-Ligand Receptor, RAGE



Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, 8(4): 306-317.

Author(s): Andrew J. Halayko and Pawan Sharma.

Affiliation: University of Manitoba, Department of Medicine, Section of Respiratory Disease, Room RS321 Respiratory Hospital, 810 Sherbrook Street, Winnipeg, MB Canada R3A 1R8.

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are persistent inflammatory conditions that have exhibited significantly increased prevalence in the past two decades. Though many current medications relieve the symptoms of obstructive airway disease, morbidity can still increase over time in individual patients. With particular respect to asthma, despite satisfactory control of symptoms in most patients with inhaled steroids, a sub-phenotype of subjects, representing ∼15% of all asthmatics, do not respond to steroids - these patients can exhibit severe asthma, which accounts for ∼50% of asthma health care costs. Moreover, inhaled steroids are not recommended as a sole therapy for COPD, and there is limited evidence for their effectiveness in preventing disease pathogenesis. Thus, it is important to better understand mechanisms for severe asthma and COPD and identify mediators released by cells, such as neutrophils, that are unresponsive to steroid therapy. This review focuses on the probable role of one the most abundant neutrophil proteins, called S100A8/A9, in asthma. S100A8/A9 is released in abundance in rheumatoid arthritis, inflammatory bowel disease and cancer, but there are no definitive studies on its role in obstructive airways disease. A primary receptor for S100A8/A9, which is uniquely expressed in high abundance in the lung, is the multi-ligand receptor for advanced glycated endproducts (RAGE) of the immunoglobin-like receptor family. RAGE participates in mediating fibroproliferative lung remodeling in idiopathic pulmonary fibrosis, and in bleomycin-exposed animal models. This review provides an overview of the S100A8/A9-RAGE axis, and discusses its potential in mediating chronic airway inflammation and tissue remodeling in asthma and COPD.

Keywords:

Airway smooth muscle, airway remodeling, neutrophils, lung, myeloid related protein, macrophage.



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Article Details

Volume: 8
Issue Number: 4
First Page: 306
Last Page: 317
Page Count: 12
DOI: 10.2174/187152309789838966
Price: $58
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