Dataset Information

The Role of Autophagy and the Chemokine (C-X-C Motif) Ligand 16 During Acute Lung Injury in Mice.

ABSTRACT: BACKGROUND Acute lung injury (ALI) is responsible for mortality in hospitalized patients. Autophagy can negatively regulate inflammatory response, and CXCL16 (chemokine (C-X-C motif) ligand 16) is a kind of chemokine, which is closely related to the inflammatory response. However, the relationship between autophagy and CXCL16 in ALI is still unclear. This study aimed to investigate the role of autophagy and chemokine CXCL16 in ALI in mice. MATERIAL AND METHODS Thirty-two male C57BL/6 mice were divided into four groups. The control group (C group) was given normal saline through intraperitoneal injection. The L group was given LPS (lipopolysaccharide) at 30 mg/kg to construct an ALI model. The 3-MA group received an intraperitoneal injection of inhibitor of autophagy 3-methyladenine at 15 mg/kg, 30 minutes before LPS injection. The anti-CXCL16 group was given 20 mg/kg of CXCL16 monoclonal antibody 30 minutes before the LPS injection. RESULTS In the 3-MA Group, the level of histological analysis, lung wet/dry ratio, total protein of BAL (bronchoalveolar lavage fluid) and TNF-a level were higher than the L group (p<0.05), the level of autophagy was lower than the L group (p<0.05), and the level of CXCL16 was higher than the L group (p<0.05). In the anti-CXCL16 group, the level of histological analysis, lung wet/dry ratio, BAL protein, and TNF-? level were declined compared to the L group (p<0.05), but there was no statistically significant difference in expression of CXCL16 detected by ELISA between the anti-CXCL16 group and the L group (p>0.05). CONCLUSIONS Autophagy played a protective role in ALI induced by LPS in mice. Autophagy could regulate the level of CXCL16. The chemokine CXCL16 could exacerbate ALI.

SUBMITTER: Gao Y

PROVIDER: S-EPMC5928852 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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The Role of Autophagy and the Chemokine (C-X-C Motif) Ligand 16 During Acute Lung Injury in Mice.

Gao Ye Y Wang Ni N Li Rui H RH Xiao Yang Z YZ

Medical science monitor : international medical journal of experimental and clinical research 20180420

BACKGROUND Acute lung injury (ALI) is responsible for mortality in hospitalized patients. Autophagy can negatively regulate inflammatory response, and CXCL16 (chemokine (C-X-C motif) ligand 16) is a kind of chemokine, which is closely related to the inflammatory response. However, the relationship between autophagy and CXCL16 in ALI is still unclear. This study aimed to investigate the role of autophagy and chemokine CXCL16 in ALI in mice. MATERIAL AND METHODS Thirty-two male C57BL/6 mice were d ...[more]

PMID: 29677174

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Project description:BackgroundPersistent acute kidney injury (AKI) portends worse clinical outcomes and remains a therapeutic challenge for clinicians. A recent study found that urinary C-C motif chemokine ligand 14 (CCL14) can predict the development of persistent AKI. We aimed to externally validate urinary CCL14 for the prediction of persistent AKI in critically ill patients.MethodsThis was a secondary analysis of the prospective multi-center SAPPHIRE study. We evaluated critically ill patients with cardiac and/or respiratory dysfunction who developed Kidney Disease: Improving Global Outcomes (KDIGO) stage 2-3 AKI within one week of enrollment. The main exposure was the urinary concentration of CCL14 measured at the onset of AKI stage 2-3. The primary endpoint was the development of persistent severe AKI, defined as ≥ 72 h of KDIGO stage 3 AKI or death or renal-replacement therapy (RRT) prior to 72 h. The secondary endpoint was a composite of RRT and/or death by 90 days. We used receiver operating characteristic (ROC) curve analysis to assess discriminative ability of urinary CCL14 for the development of persistent severe AKI and multivariate analysis to compare tertiles of urinary CCL14 and outcomes.ResultsWe included 195 patients who developed KDIGO stage 2-3 AKI. Of these, 28 (14%) developed persistent severe AKI, of whom 15 had AKI ≥ 72 h, 12 received RRT and 1 died prior to ≥ 72 h of KDIGO stage 3 AKI. Persistent severe AKI was associated with chronic kidney disease, diabetes mellitus, higher non-renal APACHE III score, greater fluid balance, vasopressor use, and greater change in baseline serum creatinine. The AUC for urinary CCL14 to predict persistent severe AKI was 0.81 (95% CI, 0.72-0.89). The risk of persistent severe AKI increased with higher values of urinary CCL14. RRT and/or death at 90 days increased within tertiles of urinary CCL14 concentration.ConclusionsThis secondary analysis externally validates urinary CCL14 to predict persistent severe AKI in critically ill patients.

Project description:Background and aimsIn extrahepatic bile duct (EHBD) cholangiopathies, including primary sclerosing cholangitis, a reactive cholangiocyte phenotype is associated with inflammation and epithelial hyperproliferation. The signaling pathways involved in EHBD injury response are poorly understood. In this study, we investigated the role of Hedgehog (HH) signaling and its downstream effectors in controlling biliary proliferation and inflammation after EHBD injury.Approach and resultsUsing mouse bile duct ligation as an acute EHBD injury model, we used inhibitory paradigms to uncover mechanisms promoting the proliferative response. HH signaling was inhibited genetically in Gli1-/- mice or by treating wild-type mice with LDE225. The role of neutrophils was tested using chemical (SB225002) and biological (lymphocyte antigen 6 complex locus G6D [Ly6G] antibodies) inhibitors of neutrophil recruitment. The cellular response was defined through morphometric quantification of proliferating cells and CD45+ and Ly6G+ immune cell populations. Key signaling component expression was measured and localized to specific EHBD cellular compartments by in situ hybridization, reporter strain analysis, and immunohistochemistry. Epithelial cell proliferation peaked 24 h after EHBD injury, preceded stromal cell proliferation, and was associated with neutrophil influx. Indian HH ligand expression in the biliary epithelium rapidly increased after injury. HH-responding cells and neutrophil chemoattractant C-X-C motif chemokine ligand 1 (CXCL1) expression mapped to EHBD stromal cells. Inhibition of HH signaling blocked CXCL1 induction, diminishing neutrophil recruitment and the biliary proliferative response to injury. Directly targeting neutrophils by inhibition of the CXCL1/C-X-C motif chemokine receptor 2/Ly6G signaling axis also decreased biliary proliferation.ConclusionsHH-regulated CXCL1 orchestrates the early inflammatory response and biliary proliferation after EHBD injury through complex cellular crosstalk.

Project description:Despite accumulating evidence on a role of immune cells and their associated chemicals in mechanisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine (C-C motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1) signaling in the rostral ventromedial medulla (RVM), a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats.An L5 spinal nerve ligation (SNL) was produced in rats under pentobarbital anesthesia. Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor (CCR2), and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein (GFAP, astroglial) and CD11b (microglial), respectively.SNL induced an increase in CCL2 expression in the RVM, and this returned to the control level at 4 weeks after injury. The induced CCL2 colocalized with NeuN, but not with GFAP and CD11b. CCR2 was also upregulated by SNL in the RVM, and this increase lasted for at least 4 weeks. CCR2 was colocalized with CD11b but not GFAP. Few RVM neurons also exhibited CCR2 staining. Neutralizing CCL2 with an anti-CCL2 antibody (0.2-20 ng) or injecting RS-102895 (0.1-10 pmol), a CCR2b chemokine receptor antagonist, into the RVM on day 1 after SNL, significantly attenuated the established thermal and mechanical hypersensitivity. In addition, injection of recombinant rat CCL2 (0.03-3 pmol) into the RVM induced dose-dependent hyperalgesia, which was prevented by pretreatment with RS-102895 (10 pmol). Interleukin-1β (IL-1β), a potent inducer of neuronal CCL2, was also selectively upregulated in RVM reactive astrocytes. Injection of IL-1β (120 fmol) into the RVM induced behavioral hyperalgesia, which was blocked by RS-102895 (10 pmol). However, an IL-1 receptor antagonist (3 pmol) did not prevent CCL2 (3 pmol)-induced hyperalgesia. These results suggest that the effect of CCL2 is downstream to IL-1β signaling.The IL-1β and CCL2-CCR2 signaling cascades play a role in neuron-glia-cytokine interactions and the descending facilitation of neuropathic pain.

Dataset Information

The Role of Autophagy and the Chemokine (C-X-C Motif) Ligand 16 During Acute Lung Injury in Mice.

Publications

The Role of Autophagy and the Chemokine (C-X-C Motif) Ligand 16 During Acute Lung Injury in Mice.

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