Airway Cytokine Pattern Predicts Severity of Asthma Symptoms During Colds

Abstract

FEBRUARY 2011 AB60 Abstracts S A T U R D A Y 221 Tranglutaminase 2 Gene Deficiency Results In Decrease Of Airway Resistance And Eosinophilic Inflammation In Murine Asthma Model H. Lee, E. Shim, J. Jung, H. Kang, H. Park, S. Kim, S. Cho, S. Chang, K. Min, Y. Kim; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, KOREA, REPUBLIC OF, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, KOREA, REPUBLIC OF, Department of Internal Medicine, Sung-Ae General Hospital, Bucheon, KOREA, REPUBLIC OF, Eulji Medical Center, Seoul, KOREA, REPUBLIC OF. RATIONALE:Transglutaminase 2(TG2) is amultifunctional calcium-dependent acyltransferase and ubiquitously expressed in mammalian tissue existing both extracellularly and intracellulary. Recent investigation reported TG2 was highly expressed in the asthmatic airways and augmented the enzymatic activity of phospholipase A2 group 3 which hydrolyzed phospholipid and release arachidonic acids. We hypothesized that TG2 would have some roles in pathogenesis of asthma. METHODS:To evaluate expression of TG2 in asthma patients, we stained lung tissue with anti-TG2 antibody and detected TG2mRNA expression in induced sputum samples of asthmatic patients. To see the effect of TG2 deficiency, wemade a murine ovalbumin (OVA) asthmamodel with TG2 null mice and compared with wild type mice. Airway hyperresponsivenss (AHR) to methacholine, airway inflammatory cells, and cytokines in homogenate of lung tissue were evaluated. RESULTS: TG2 expression in bronchial epithelium and TG2mRNA level in induced sputum samples were increased in asthmatics compared with normal controls. TG2 null mice showed significant reduction in eosinophilic airway inflammation, AHR, serum OVA-specific IgG1/G2a ratio and Th2 cytokines (IL-4, IL-13) in lung homogenates compared with WT mice after OVA challenge. CONCLUSIONS: In human asthmatics, TG2 is highly expressed in airway epithelium and induced sputum. In murine asthma model, TG2 deficiency effectively reverses airway hyperresponsiveness and eosinophilic airway inflammation, Th2 immune responses. These findings suggest that TG2 play important roles in the pathogenesis of asthma.