AUTHOR=Ferreira Jorge M. C. , Huhle Robert , Müller Sabine , Schnabel Christian , Mehner Mirko , Koch Thea , Gama de Abreu Marcelo 

TITLE=Static Stretch Increases the Pro-Inflammatory Response of Rat Type 2 Alveolar Epithelial Cells to Dynamic Stretch

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.838834

DOI=10.3389/fphys.2022.838834

ISSN=1664-042X

ABSTRACT=<p><bold>Background</bold>: Mechanical ventilation (MV) inflicts stress on the lungs, initiating or increasing lung inflammation, so-called ventilator-induced lung injury (VILI). Besides overdistention, cyclic opening-and-closing of alveoli (atelectrauma) is recognized as a potential mechanism of VILI. The dynamic stretch may be reduced by positive end-expiratory pressure (PEEP), which in turn increases the static stretch. We investigated whether static stretch modulates the inflammatory response of rat type 2 alveolar epithelial cells (AECs) at different levels of dynamic stretch and hypothesized that static stretch increases pro-inflammatory response of AECs at given dynamic stretch.</p><p><bold>Methods:</bold> AECs, stimulated and not stimulated with lipopolysaccharide (LPS), were subjected to combinations of static (10, 20, and 30%) and dynamic stretch (15, 20, and 30%), for 1 and 4 h. Non-stretched AECs served as control. The gene expression and secreted protein levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 2 (MIP-2) were studied by real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The effects of static and dynamic stretch were assessed by two-factorial ANOVA with planned effects post-hoc comparison according to Šidák. Statistical significance was considered for <italic>p</italic> &lt; 0.05.</p><p><bold>Results:</bold> In LPS-stimulated, but not in non-stimulated rat type 2 AECs, compared to non-stretched cells: 1) dynamic stretch increased the expression of amphiregulin (AREG) (<italic>p</italic> &lt; 0.05), MCP-1 (<italic>p</italic> &lt; 0.001), and MIP-2 (&lt;0.05), respectively, as well as the protein secretion of IL-6 (<italic>p</italic> &lt; 0.001) and MCP-1 (<italic>p</italic> &lt; 0.05); 2) static stretch increased the gene expression of MCP-1 (<italic>p</italic> &lt; 0.001) and MIP-2, but not AREG, and resulted in higher secretion of IL-6 (<italic>p</italic> &lt; 0.001), but not MCP-1, while MIP-2 was not detectable in the medium.</p><p><bold>Conclusion:</bold> In rat type 2 AECs stimulated with LPS, static stretch increased the pro-inflammatory response to dynamic stretch, suggesting a potential pro-inflammatory effect of PEEP during mechanical ventilation at the cellular level.</p>