Remote ischemic preconditioning ameliorates indirect acute lung injury by modulating phosphorylation of IκBα in mice

Abstract

Objective Acute lung injury is responsible for mortality in seriously ill patients. Previous studies have shown that systemic inflammation is attenuated by remote ischemic preconditioning (RIPC) via reducing nuclear factor-kappa B (NF-κB). Therefore, we investigated whether lipopolysaccharide (LPS)-induced indirect acute lung injury (ALI) can be protected by RIPC. Methods RIPC was accomplished by 10 minutes of occlusion using a tourniquet on the right hind limb of mice, followed by 10 minutes of reperfusion. This process was repeated three times. Intraperitoneal LPS (20 mg/kg) was administered to induce indirect ALI. Inflammatory cytokines in bronchoalveolar lavage fluid were analyzed using an enzyme-linked immunosorbent assay. Pulmonary tissue was excised for histological examination, and for examining NF-κB activity and phosphorylation of inhibitor of κBα (IκBα). Results NF-κB activation and LPS-induced histopathological changes in the lungs were significantly alleviated in the RIPC group. RIPC reduced phosphorylation of IκBα in lung tissue of ALI mice. Conclusions RIPC attenuates endotoxin-induced indirect ALI. This attenuation might occur through modification of NF-κB mediation of cytokines by modulating phosphorylation of IκBα.

Preconditioning mesenchymal stromal cells with flagellin enhances the anti‑inflammatory ability of their secretome against lipopolysaccharide‑induced acute lung injury

“…An LPS-induced ALI mouse model was used in the present study, as its reliability and reproducibility have been previously confirmed ( 42 ). The results of the examination of the lung exudate, H&E staining and cell counting in the BALF identified that both CM and F-CM significantly prevented LPS-induced lung injury in mice, and the effects of F-CM treatment were superior.…”

Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response

“…NLRP3 inflammasome activation results in caspase mediated cell death [ 119 ]. Several studies haves demonstrated that RIC modulates NF-κB activity via in both ischaemia and endotoxaemia [ 74 , 76 , 92 , 117 , 130 ]. TLR4 Toll-like receptor 4, DAMPS damage associated molecular patterns, HMGB1 high mobility group box 1, TNF-α tumour necrosis factor alpha, LPS lipopolysaccharide, RAGE Receptor for advanced glycation end-products, ERK extracellular signal related kinase, MAPK mitogen activated protein kinase, EGR-1 early growth response 1, TAK1 transforming factor-β-activated kinase 1, Iκβ inhibitor kappa beta kinase, NF-κβ nuclear factor kappa beta …”

“…RIC reduces inflammatory cytokine levels and improves survival in rodent models of lipopolysaccharide (LPS) induced endotoxaemia [ 68 , 74 , 76 ]. In mice receiving three cycles of hind limb I/R (10 min ischaemia/10 min reperfusion) prior to LPS exposure, there was a significant survival benefit from RIC (10% of the control group survived vs 60% of the intervention group; p < 0.001 ).…”

“…In the same study, histology revealed a reduction in the diffuse parenchymal pulmonary inflammation associated with LPS-induced acute lung injury, and a reduction of cytokines in bronchoalveolar fluid (TNF -α , IL-1β and IL-6). It was further demonstrated that RIC mediates cytokine reduction via a downregulation of NF-κB and myeloperoxidase (MPO) pathways [ 76 ]. MPO is associated with increased neutrophil influx to areas of inflammation and, therefore, promotes the release of pro-inflammatory cytokines from neutrophils, which are sentinel cells in the inflammatory response [ 78 ].…”

“…dexamethasone can interact with inhibitors of NF-κβ, to reduce cytokines and the inflammatory response [ 146 ]. It is interesting then to note that RIC has also modified Iκβα proteins in a rodent model of acute lung injury, leading to reduced activity of NF-κβ and reduced TNF-α, IL-1β and IL-6 secretion [ 76 ].…”