PMID- 35480037 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1664-042X (Print) IS - 1664-042X (Electronic) IS - 1664-042X (Linking) VI - 13 DP - 2022 TI - Static Stretch Increases the Pro-Inflammatory Response of Rat Type 2 Alveolar Epithelial Cells to Dynamic Stretch. PG - 838834 LID - 10.3389/fphys.2022.838834 [doi] LID - 838834 AB - Background: 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. Methods: 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 Sidak. Statistical significance was considered for p < 0.05. Results: 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) (p < 0.05), MCP-1 (p < 0.001), and MIP-2 (<0.05), respectively, as well as the protein secretion of IL-6 (p < 0.001) and MCP-1 (p < 0.05); 2) static stretch increased the gene expression of MCP-1 (p < 0.001) and MIP-2, but not AREG, and resulted in higher secretion of IL-6 (p < 0.001), but not MCP-1, while MIP-2 was not detectable in the medium. Conclusion: 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. CI - Copyright (c) 2022 Ferreira, Huhle, Muller, Schnabel, Mehner, Koch and Gama de Abreu. FAU - Ferreira, Jorge M C AU - Ferreira JMC AD - Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. FAU - Huhle, Robert AU - Huhle R AD - Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. FAU - Muller, Sabine AU - Muller S AD - Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. FAU - Schnabel, Christian AU - Schnabel C AD - Department of Anesthesiology and Intensive Care Medicine, Clinical Sensoring and Monitoring Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. FAU - Mehner, Mirko AU - Mehner M AD - Department of Anesthesiology and Intensive Care Medicine, Clinical Sensoring and Monitoring Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. FAU - Koch, Thea AU - Koch T AD - Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. FAU - Gama de Abreu, Marcelo AU - Gama de Abreu M AD - Department of Anesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, University Hospital Carl Gustav Carus Dresden at Technische Universitat Dresden, Dresden, Germany. AD - Department of Intensive Care and Resuscitation, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, United States. AD - Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, United States. LA - eng PT - Journal Article DEP - 20220411 PL - Switzerland TA - Front Physiol JT - Frontiers in physiology JID - 101549006 PMC - PMC9035495 OTO - NOTNLM OT - VILI OT - alveolar epithelial cells type 2 OT - dynamic stretch OT - inflammation OT - modulation OT - static stretch COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/04/29 06:00 MHDA- 2022/04/29 06:01 PMCR- 2022/04/11 CRDT- 2022/04/28 06:25 PHST- 2021/12/18 00:00 [received] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/04/28 06:25 [entrez] PHST- 2022/04/29 06:00 [pubmed] PHST- 2022/04/29 06:01 [medline] PHST- 2022/04/11 00:00 [pmc-release] AID - 838834 [pii] AID - 10.3389/fphys.2022.838834 [doi] PST - epublish SO - Front Physiol. 2022 Apr 11;13:838834. doi: 10.3389/fphys.2022.838834. eCollection 2022.