Alveolar Macrophages Mediate Allergic Airway Inflammation In The Obese-asthma Models

Abstract

FEBRUARY 2011 AB62 Abstracts S A T U R D A Y 229 Glutamate Enhances Amphiregulin (AREG) Production from Human Airway Smooth Muscle Cells K. Orihara, V. Anaparti, P. Sharma, A. Matsuda, K. Matsumoto, H. Saito, A. Halayko, R. Moqbel; University of Manitoba, Winnipeg, MB, CANADA, National Research Institute for Child Health & Development, Tokyo, JAPAN. RATIONALE: Severe and corticosteroid refractory asthma are associated with increase in the expression of epidermal growth factor receptor (EGFR). Recent attention has focused on the role of a comparatively new molecule, AREG, a member of the epithelial growth factor (EGF) family in asthma. Sputum AREG levels are significantly higher in asthmatics than in patients with various respiratory tract infections or healthy controls. AREG levels correlate negatively with airway hyperresponsiveness. Glutamate, a most common neurotransmitter in the central nervous system, has also been shown to be associated with immune system, autoimmune diseases as well as allergy and asthma. METHODS: Airway smooth muscle (ASM) cells were obtained from consenting non-asthmatic donor airways. ASM cells were expanded in DMEM+10% FBS and treated with F12+ITS before harvesting RNA and supernatant on day 3. Expression of AREGmRNA and protein was detected using quantative real-time PCR and ELISA, respectively. RESULTS: Glutamate enhanced AREG production from ASM cells, in vitro, following treatment with TGF-b1+TNF+IL-4, which mimics chronic inflammatory asthmatic conditions. The glutamate effect was shown to occur through glutamate/N-methyl-D-aspartate (NMDA) receptors, as antagonizing the latter usingMK-801, a specific NMDA-R blocker, abrogated the increase in AREG levels. In addition, AREG level was further enhanced with b2-agonist, and was not inhibited by corticosteroid treatment. CONCLUSIONS: High AREG concentrations were produced by ASM cells treated with glutamate in chronic Th2 inflammatory cytokine conditions. Since Th2, but not Th1 cells are able to produce AREG, this protein may play a role in airway remodeling during chronic asthma.