LSC Abstract – Alpha1-antitrypsin reduces inflammation and endoplasmic reticulum stress in lung epithelial cells in vitro

Endoplasmic Reticulum stress (ER stress) plays an important role in initiation of the inflammatory response in the lung. In the present study we investigate the effects of Alpha1-Antitrypsin (AAT) on the ER stress response, inflammation and lung epithelial wound healing.We hypothesize that AAT restores ER homeostasis and reduces inflammation in bronchial and alveolar epithelial cells. Bronchial epithelial cells B2B and alveolar epithelial-like cells A549 were treated with Tunicamycin (TN) to induce ER stress, followed by treatment AAT. ER stress markers: Grp78, XBP1 and CHOP where measured by RT PCR. ELISA was performed to measure the inflammatory markers and wound healing was measured over time. Gene expression of ER stress markers was significantly reduced after AAT treatment compared to placebo: Grp78 (49.43±16.61 vs 105.87±11.76), XBP1 (34.00±6.22 vs 107.2±24.12), CHOP (58.93±15.54 vs 297.2±39.58) in A549 cells and Grp78 (42.77±9.95 vs 789.20±9.28), XBP1 (37.33±5.114 vs 120.5±14.58), CHOP (48.93±5.53 vs 307.2±31.35) in B2B cells. Levels of IL-6 in cells treated with AAT decreased significantly in A549 (193.8±16.01 vs 1321±120.2), in B2B (193.8±16.01 vs 1388±167.3). In accordance, IL-8 decreased significantly after AAT treatment for A549 (36.17±8.78 vs 93.90±1.044) and for B2B (36.17±8.78 vs 122.3±28.55). AAT increased epithelial wound healing in ER stressed B2B and A549 cells (25%+/-SD vs 18%+/-SD). AAT treatment decreases ER stress and inflammation and improves wound repair in both alveolar epithelial and bronchial epithelial cells.