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

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

Volume: 8 Issue: 4

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

Affiliation:

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

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.

Cite this article as:

Halayko J. Andrew and Sharma Pawan, 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 2009; 8 (4) . https://dx.doi.org/10.2174/187152309789838966