“…In contrast, hypoxia is protective against oxidant-induced loss of barrier integrity (Olson et al, 2011); however, our observations indicate that the stabilization of HIF-1α protein alone (Figure 5) is not sufficient to prevent the loss of barrier integrity following liquid application. Epithelial barrier integrity is also adversely affected following exposure to a diverse range of inhaled substances including diesel exhaust particulates, ambient particulate matter, acrolein, asbestos, ozone, wood smoke particulates, and e-cigarette flavorings (Peterson et al, 1993;Yu et al, 1994;Olson et al, 2011;Gerloff et al, 2017;Xiong et al, 2018;Zeglinski et al, 2019;Smyth et al, 2020;Xian et al, 2020;Bowers et al, 2022). Thus, the observation that liquid application alone significantly reduces barrier integrity indicates the potential for this manner of dosing to limit the sensitivity of this approach to identify test substances that disrupt barrier function.…”