TY - JOUR T1 - TRPA1 mediates cigarette smoke-induced TNFa secretion in macrophages JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2021.PA2320 VL - 58 IS - suppl 65 SP - PA2320 AU - Denis Naumov AU - Ivana Sugaylo AU - Dina Gassan AU - Olesya Kotova AU - Evgeniya Afanaseva AU - Elizaveta Sheludko AU - Yana Gorchakova Y1 - 2021/09/05 UR - http://erj.ersjournals.com/content/58/suppl_65/PA2320.abstract N2 - Background: Along with epithelium, alveolar macrophages are among the first cells encountering smoke and airborne particles in the respiratory system. It has been shown that TRPA1 cation channels expressed on macrophages may serve as receptors for cigarette smoke (CS) chemical compounds.Objectives: The aim of the study was to investigate the role of TRPA1 in CS-induced cytokine secretion by macrophages.Methods: Macrophages were differentiated from blood monocytes of healthy donors (n=5) in the presence of 50 ng/ml GM-CSF. CS extract (CSE) was prepared by bubbling the smoke from two cigarettes through 20 ml of RPMI-1640 at 8 ml/s. Cells were exposed to 4% CSE alone or in presence of 100 μM HC-030031 (TRPA1 antagonist) for 24 h. TNFα, IL-1β, IL-6 and IL-8 were measured in culture media supernatants by multiplex assay.Results: CSE significantly increased TNFα production (66.6 (52.9-90.3) pg/ml vs. 123.9 (117.6-155.8) pg/ml, p=0.04). The presence of HC-030031 completely prevented CSE-induced secretion of TNFα (123.9 (117.6-155.8) pg/ml vs. 62.0 (60.9-71.3) pg/ml, p=0.04). Besides, we observed a tendency to increase in IL-8 concentration in response to CSS (5586.6 (5037.4-57.55.2) pg/ml vs. 5699.8 (5452.4-6202.2) pg/ml, p=0.07) which was also attenuated by HC-030031 (5306.6 (5225.2-5508.6) pg/ml, p=0.13). CSE did not significantly affect IL-1β and IL-6 levels, however, HC-030031 unexpectedly raised IL-1β production (16.2 (15.3-16.3) pg/ml vs. 23.7 (22.8-27.2) pg/ml, p=0.04).Conclusions: We established that TRPA1 may mediate CSE-induced secretion of TNFα and possibly IL-8 by macrophages. At the same time, constitutive activity of TRPA1 seems to inhibit basal IL-1β production.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA2320.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -