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Emodin ameliorates acute pancreatitis-induced lung injury by suppressing NLRP3 inflammasome-mediated neutrophil recruitment.

ABSTRACT: Severe acute pancreatitis (SAP) activates the systemic inflammatory response and is potentially lethal. The aim of the present study was to determine the effects of emodin on acute lung injury (ALI) in rats with SAP and investigate the role of the Nod-like receptor protein 3 (NLRP3) inflammasome and its association with neutrophil recruitment. Sodium taurocholate (5.0%) was used to establish the SAP model. All animals were randomly assigned into four groups: Sham, SAP, emodin and dexamethasone (positive control drug) groups (n=10 mice per group). Histopathology observation of pancreatic and lung tissues was detected by hematoxylin and eosin staining. The levels of serum amylase, IL-1β and IL-18 were measured by ELISA. Single-cell suspensions were obtained from enzymatically digested lung tissues, followed by flow cytometric analysis for apoptosis. In addition, the expression levels of NLRP3 inflammasome-associated and apoptosis-associated proteins in lung tissues were measured by western blotting. Moreover, lymphocyte antigen 6 complex locus G6D⁺ (Ly6G⁺) cell recruitment was detected using immunohistochemical analysis. The results revealed that emodin markedly improved pancreatic histological injury and decreased the levels of serum amylase, IL-1β and IL-18. Pulmonary edema and apoptosis were significantly alleviated by emodin. Additionally, the protein expression levels of intercellular adhesion molecule 1, NLRP3, apoptosis-associated speck-like protein containing a CARD and cleaved caspase-1 were downregulated following emodin treatment. Moreover, emodin inhibited Ly6G⁺ cell recruitment in lung tissues. The present study demonstrated that emodin may offer protection against ALI induced by SAP via inhibiting and suppressing NLRP3 inflammasome-mediated neutrophil recruitment and may be a novel therapeutic strategy for the clinical treatment of ALI.

SUBMITTER: Jiang N

PROVIDER: S-EPMC8220649 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation.MethodsReactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed.ResultsCellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells.ConclusionTaken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.

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Emodin ameliorates acute pancreatitis-induced lung injury by suppressing NLRP3 inflammasome-mediated neutrophil recruitment.

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