ASC plays a role in alveolar epithelial integrity

Abstract

Apoptosis‐associated speck‐like protein containing a carboxy‐terminal CARD (ASC) is one of the major components of the NLRP3 inflammasome. We previously reported that inflammsome plays a role in macrophage activation under oxidant stress. In contrast to the widely studied inflammasome component NLRP3, the role of ASC under conditions of oxidant stress remains elusive. In this study, we tested the hypothesis that ASC deficiency in alveolar macrophages would lead to blunted inflammatory cytokine secretion and modified alveolar epithelial cell (A549) integrity. To test this, we used bone marrow‐derived macrophages (BMMs) harvested from wild type and ASC−/− mice. BMMs were subjected to hyperoxic conditions in the presence or absence of LPS. Supernatants from these cells were used to treat A549 cells and transepitheleal resistance (TER) was measured. Further, protein expression of E‐cadherin by A549 cells exposed to BMM‐derived supernatants was used as a measure of epithelial integrity. Our results reveal that A549 cells treated with ASC−/− BMM supernatant under hyperoxic conditions showed decreased TER in comparison to WT BMM supernatant treatment. The expression of E‐cadherin in these cells was also decreased in comparison to WT hyperoxic control. These results suggest that ASC may play a role in aiding alveolar macrophages maintaining epithelial integrity under oxidant stress.