Journal of Inflammation-London最新文献

{"title":"Finding the priority and cluster of inflammatory biomarkers for infectious preterm birth: a systematic review.","authors":"Jiayi Li,&nbsp;Jianrong Ge,&nbsp;Na Ran,&nbsp;Changwu Zheng,&nbsp;Yumeng Fang,&nbsp;Danna Fang,&nbsp;Qian Yang,&nbsp;Yeling Ma","doi":"10.1186/s12950-023-00351-0","DOIUrl":"https://doi.org/10.1186/s12950-023-00351-0","url":null,"abstract":"<p><p>Infectious preterm birth (PTB) is one of the most important causes of perinatal death. It is difficult to find reliable biomarkers accurate to gestational weeks for infectious PTB prediction clinically. Infectious PTB is found usually accompanied with immune imbalance. Thus, the systematic study to find the priority of inflammatory biomarkers and innovative inflammatory clusters for infectious PTB prediction is urgently needed.This systematic study that focused on the inflammatory clusters and infectious PTB in the PubMed database was analyzed by using the criteria of the Population, Intervention, Comparison, Outcome, and Study design (PICOS) framework according to the recommendations of preferred reporting items for systematic reviews and meta-analysis (PRISMA).The network meta-analyzed results showed that the prioritization of the inflammatory factors for infectious PTB prediction is soluble tumor necrosis factor receptor 2 (sTNFR2) > tumor necrosis factor α (TNFα) > interleukin-10 (IL-10) > interleukin-6 (IL-6) > C-reactive protein (CRP) > interleukin-1β (IL-1β). Furthermore, the results also indicated that global consideration of multiple inflammatory factors, such as CRP/IL-1β/IL-6 biomarker cluster in gestational 27-34 weeks, and the tumor necrosis factor/nerve growth factor (TNF/NGF) family during gestational 25-33 weeks, were potential biomarker clusters that specific for infectious PTB prediction.This study systematically pointed out prioritization of the inflammatory factors for infectious PTB prediction. The results also provided evidence that maternal inflammatory clusters can predict infectious PTB occurrence at accurate gestational week. The global consideration of multiple inflammatory factors at accurate gestational age is highlighted.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"25"},"PeriodicalIF":5.1,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10367376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of GSK3β activity alleviates acute liver failure via suppressing multiple programmed cell death.","authors":"Danmei Zhang, Chunxia Shi, Qingqi Zhang, Yukun Wang, Jin Guo, Zuojiong Gong","doi":"10.1186/s12950-023-00350-1","DOIUrl":"10.1186/s12950-023-00350-1","url":null,"abstract":"<p><strong>Background: </strong>Acute liver failure (ALF) is one of the most common life-threatening diseases in adults without previous liver disease. Glycogen synthase kinase 3β (GSK3β) is a serine/threonine protein kinase that is widely distributed in the cells. Inhibition of its activity can inhibit cell death and promote autophagy through various pathways, thus providing a protective effect. In this study, we aimed to investigate the effect on ALF after inhibition of GSK3β and its potential mechanisms.</p><p><strong>Methods: </strong>D- galactosamine(D-Gal) in combination with lipopolysaccharide(LPS) was used to induce ALF in vitro and in vivo. And then GSK3β inhibitor TDZD-8 was used to explore the protective effect against ALF. After TDZD-8 treatment TUNEL staining and flow techniques were used to detect the proportion of apoptosis in liver tissues and cells respectively, while western blotting and immunofluorescence assays were performed to detect the expression levels of apoptosis, pyroptosis and necroptosis-related proteins in tissues and cells. In addition, western blotting was performed to explore the specific mechanism of hepatoprotective effect after GSK3β inhibition to detect the expression levels of TAK1, TRAF6 and HDAC3 after TRAF6 and HDAC3 inhibition alone. The co-localization of TRAF6 and HDAC3 in vitro was detected by immunofluorescence, while the interaction between TRAF6 and HDAC3 was detected by immunoprecipitation assay.</p><p><strong>Results: </strong>Both in vivo and in vitro experiments, GSK3β inhibitor TDZD-8 can significantly alleviate the progression of ALF. Inhibition of GSK3β activity could significantly reduce the level of hepatocyte apoptosis, pyroptosis, necroptosis and improve liver dysfunction and tissue damage. Furthermore, we found that hepatocyte TAK1 and TRAF6 levels decreased and HDAC3 levels increased in ALF, whereas inhibition of GSK3β upregulated TAK1 and TRAF6 levels and decreased HDAC3 expression.</p><p><strong>Conclusion: </strong>GSK3β inhibitor TDZD-8 can prevent the progression of ALF, and its action may involve the TRAF6/HDAC3/TAK1 pathway.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"24"},"PeriodicalIF":5.1,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10347874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9818509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The occurrence and development of radiation-induced lung injury after interstitial brachytherapy and stereotactic radiotherapy in SD rats.","authors":"Zhuo Chen,&nbsp;Bin Wang,&nbsp;Zhouxue Wu,&nbsp;Hua Xiao,&nbsp;Yang Yang,&nbsp;Junying Fan,&nbsp;Yingjiang Gu,&nbsp;Chuan Chen,&nbsp;Jingbo Wu","doi":"10.1186/s12950-023-00348-9","DOIUrl":"https://doi.org/10.1186/s12950-023-00348-9","url":null,"abstract":"<p><strong>Background: </strong>To compare the severity of radiation-induced lung injury (RILI) after the right lung of SD rats received interstitial brachytherapy and stereotactic radiotherapy (SBRT).</p><p><strong>Methods: </strong>RILI rat model was established using interstitial brachytherapy and SBRT methods, respectively. CT scan was performed to analyze the lung volume and the CT value difference between the left and right lungs in rats. Then the lung tissues were analyzed through H&E staining, peripheral blood was extracted to detect the expression levels of serum inflammatory cytokines, pro-fibrotic cytokines, and fibrotic-inhibiting cytokines by ELISA.</p><p><strong>Results: </strong>The difference between right and left lung CT values was significantly elevated in the SBRT group when compared with the control group and the interstitial brachytherapy group (P < 0.05). The IFN-γ expression in the interstitial brachytherapy group was significantly different from that in the SBRT group at week 1, 4, 8 and 16. Besides, the expressions of IL-2, IL-6 and IL-10 in SBRT group were significantly higher than that of interstitial brachytherapy group (P < 0.05). The TGF-β expression in interstitial brachytherapy group reached its peak with the increase of time from week 1 to week 16, and it was significantly lower than SBRT group (P < 0.05). The mortality rate in the SBRT group was 16.7%, which was significantly higher than that in the interstitial brachytherapy group.</p><p><strong>Conclusion: </strong>The treatment method of interstitial brachytherapy is considered as an effective and safe tool by reducing the side effects of radiotherapy and increasing the radiation dose of radiotherapy.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"23"},"PeriodicalIF":5.1,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10332105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell-derived brainstem mouse astrocytes obtain a neurotoxic phenotype in vitro upon neuroinflammation.","authors":"Caroline Lindblad, Susanne Neumann, Sólrún Kolbeinsdóttir, Vasilios Zachariadis, Eric P Thelin, Martin Enge, Sebastian Thams, Lou Brundin, Mikael Svensson","doi":"10.1186/s12950-023-00349-8","DOIUrl":"10.1186/s12950-023-00349-8","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes respond to injury and disease through a process known as reactive astrogliosis, of which inflammatory signaling is one subset. This inflammatory response is heterogeneous with respect to the inductive stimuli and the afflicted central nervous system region. This is of plausible importance in e.g. traumatic axonal injury (TAI), where lesions in the brainstem carries a particularly poor prognosis. In fact, astrogliotic forebrain astrocytes were recently suggested to cause neuronal death following axotomy. We therefore sought to assess if ventral brainstem- or rostroventral spinal astrocytes exert similar effects on motor neurons in vitro.</p><p><strong>Methods: </strong>We derived brainstem/rostroventral spinal astrocyte-like cells (ES-astrocytes) and motor neurons using directed differentiation of mouse embryonic stem cells (ES). We activated the ES-astrocytes using the neurotoxicity-eliciting cytokines interleukin- (IL-) 1α and tumor necrosis factor-(TNF-)α and clinically relevant inflammatory mediators. In co-cultures with reactive ES-astrocytes and motor neurons, we assessed neurotoxic ES-astrocyte activity, similarly to what has previously been shown for other central nervous system (CNS) regions.</p><p><strong>Results: </strong>We confirmed the brainstem/rostroventral ES-astrocyte identity using RNA-sequencing, immunocytochemistry, and by comparison with primary subventricular zone-astrocytes. Following cytokine stimulation, the c-Jun N-terminal kinase pathway down-stream product phosphorylated c-Jun was increased, thus demonstrating ES-astrocyte reactivity. These reactive ES-astrocytes conferred a contact-dependent neurotoxic effect upon co-culture with motor neurons. When exposed to IL-1β and IL-6, two neuroinflammatory cytokines found in the cerebrospinal fluid and serum proteome following human severe traumatic brain injury (TBI), ES-astrocytes exerted similar effects on motor neurons. Activation of ES-astrocytes by these cytokines was associated with pathways relating to endoplasmic reticulum stress and altered regulation of MYC.</p><p><strong>Conclusions: </strong>Ventral brainstem and rostroventral spinal cord astrocytes differentiated from mouse ES can exert neurotoxic effects in vitro. This highlights how neuroinflammation following CNS lesions can exert region- and cell-specific effects. Our in vitro model system, which uniquely portrays astrocytes and neurons from one niche, allows for a detailed and translationally relevant model system for future studies on how to improve neuronal survival in particularly vulnerable CNS regions following e.g. TAI.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"22"},"PeriodicalIF":4.4,"publicationDate":"2023-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10097010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ischemic stroke-related gene expression profiles across species: a meta-analysis.","authors":"Ruslan Rust","doi":"10.1186/s12950-023-00346-x","DOIUrl":"https://doi.org/10.1186/s12950-023-00346-x","url":null,"abstract":"<p><p>Stroke patients are often left with permanent disabilities with no regenerative treatment options. Unbiased RNA sequencing studies decoding the transcriptional signature of stroked tissue hold promise to identify new potential targets and pathways directed to improve treatment for stroke patients. Here, gene expression profiles of stroked tissue across different time points, species, and stroke models were compared using NCBI GEO database. In total, 34 datasets from mice, rats, humans, and primates were included, exploring gene expression differences in healthy and stroked brain tissue. Distinct changes in gene expression and pathway enrichment revealed the heterogenicity of the stroke pathology in stroke-related pathways e.g., inflammatory responses, vascular repair, remodelling and cell proliferation and adhesion but also in diverse general, stroke-unrelated pathways that have to be carefully considered when evaluating new promising therapeutic targets.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"21"},"PeriodicalIF":5.1,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9708950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of AT7519 as a pro-resolution compound in an acetaminophen-induced mouse model of acute inflammation by UPLC-MS/MS.","authors":"Jennifer A Cartwright, Joanna P Simpson, Natalie Z M Homer, Adriano G Rossi","doi":"10.1186/s12950-023-00345-y","DOIUrl":"10.1186/s12950-023-00345-y","url":null,"abstract":"<p><strong>Background: </strong>Uncontrolled inflammation contributes to the progression of organ damage in acute conditions, such as acetaminophen-induced acute liver injury (APAP-ALI) and there are limited treatments for this condition. AT7519, a cyclic-dependent kinase inhibitor (CDKI), has been used successfully in several conditions, to resolve inflammation and return tissue homeostatic functions. AT7519 has not been assessed in APAP-ALI and its effect on APAP metabolism is unknown. Targeted chromatography and mass spectrometry can be used to assess multiple compounds simultaneously and this approach has not been applied yet to measure APAP and AT7519 in a mouse model.</p><p><strong>Results: </strong>We show an optimised simple and sensitive LC-MS/MS method for determining concentrations of AT7519 and APAP in low volumes of mouse serum. Using positive ion mode electrospray ionisation, separation of AT7519 and APAP and their corresponding isotopically labelled internal standards [²H]₈-AT16043M (d8-AT7519) and [²H]₈-APAP (d4-APAP), was achieved on an Acquity UPLC BEH C18 column (100 × 2.1 mm; 1.7μm). A gradient mobile phase system of water and methanol was delivered at a flow rate of 0.5 mL/min with a run time of 9 min. Calibration curves were linear, intra-day and inter-day precision and accuracy were acceptable and the covariates of all standards and quality control replicates were less than 15%. The method was successfully applied to evaluate AT7519 and APAP levels 20 h post AT7519 (10 mg/mg) in C57Bl6J wild type mouse serum treated with either vehicle or APAP. Serum AT7519 was significantly higher in mice that had received APAP compared to control, but there was no correlation between APAP and AT7519 quantification. There was also no correlation of AT7519 and hepatic damage or proliferation markers.</p><p><strong>Conclusion: </strong>We optimised an LC-MS/MS method to quantify both AT7519 and APAP in mouse serum (50 µL), using labelled internal standards. Application of this method to a mouse model of APAP toxicity proved effective in accurately measuring APAP and AT7519 concentrations after i.p. dosing. AT7519 was significantly higher in mice with APAP toxicity, indicating hepatic metabolism of this CDKI, but there was no correlation with markers of hepatic damage or proliferation, demonstrating that this dose of AT7519 (10 mg/kg) does not contribute to hepatic damage or repair. This optimised method can be used for future investigations of AT7519 in APAP in mice.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"20"},"PeriodicalIF":4.4,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10251596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10010016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of biomarkers related to Th1 cell infiltration in neuropathic pain.","authors":"Xiangsheng Zhang,&nbsp;Jiurong Cheng,&nbsp;Yingdong Deng,&nbsp;Caiyun Guo,&nbsp;Yu Cao,&nbsp;Suo Wang,&nbsp;Chenxi Zhou,&nbsp;Ziqiang Lin,&nbsp;Simin Tang,&nbsp;Jun Zhou","doi":"10.1186/s12950-023-00343-0","DOIUrl":"https://doi.org/10.1186/s12950-023-00343-0","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a widespread chronic pain with a prevalence of 6.9-10% in the general population, severely affecting patients' physical and mental health. Accumulating evidence indicated that the immune environment is an essential factor causing NP. However, the mechanism is unclear. This study attempted to analyze NP-related immune infiltration patterns. We downloaded the expression profiles from the Gene Expression Omnibus (GEO) database. The novel method of single-sample gene set enrichment analysis (ssGSEA) algorithm and weighted gene co-expression network analysis (WGCNA) was applied to identify immune-related genes and verified in vitro and in vivo experiments. The spared nerve injury (SNI) group was closely related to type1 T helper cells (Th1 cells), and two key genes (Abca1 and Fyb) positively correlated with Th1 cell infiltration. At the single-cell level, Abca1 and Fyb were significantly expressed in macrophages. In addition, we verified that Abca1 could affect the function of macrophages. Finally, we hypothesized that Abca1 is involved in the infiltration of Th1 cells into dorsal root ganglion (DRG) tissues and induces NP via immunoinflammatory response. Hence, the present study aimed to elucidate the correlation between NP and neuroinflammation and identify a new therapeutic target for treating NP.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"19"},"PeriodicalIF":5.1,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10236848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9564834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated endothelial cell markers in systemic lupus erythematosus: a systematic review and meta-analysis.","authors":"S C Bergkamp,&nbsp;M J Wahadat,&nbsp;A Salah,&nbsp;T W Kuijpers,&nbsp;V Smith,&nbsp;S W Tas,&nbsp;J M van den Berg,&nbsp;S Kamphuis,&nbsp;D Schonenberg-Meinema","doi":"10.1186/s12950-023-00342-1","DOIUrl":"https://doi.org/10.1186/s12950-023-00342-1","url":null,"abstract":"<p><strong>Objectives: </strong>To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE.</p><p><strong>Methods: </strong>Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman's rank or Pearson's) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used.</p><p><strong>Results: </strong>From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin.</p><p><strong>Conclusions: </strong>We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"18"},"PeriodicalIF":5.1,"publicationDate":"2023-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10189957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9486928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil extracellular traps in acute coronary syndrome.","authors":"Yawen Wu,&nbsp;Shilin Wei,&nbsp;Xiangyang Wu,&nbsp;Yongnan Li,&nbsp;Xue Han","doi":"10.1186/s12950-023-00344-z","DOIUrl":"https://doi.org/10.1186/s12950-023-00344-z","url":null,"abstract":"<p><p>Acute coronary syndrome (ACS) is a group of clinical syndromes caused by acute myocardial ischemia, which can cause heart failure, arrhythmia and even sudden death. It is the major cause of disability and death worldwide. Neutrophil extracellular traps (NETs) are reticular structures released by neutrophils activation and have various biological functions. NETs are closely related to the occurrence and development of ACS and also the subsequent damage after myocardial infarction. The mechanisms are complex and interdependent on various pathways, which require further exploration. This article reviewed the role and mechanism of NETs in ACS, thereby providing a valuable reference for the diagnosis and clinical treatment of ACS.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"17"},"PeriodicalIF":5.1,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9803795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PKM2/STAT1-mediated PD-L1 upregulation on neutrophils during sepsis promotes neutrophil organ accumulation by serving an anti-apoptotic role.","authors":"Yinjiaozhi Li, Ruoming Tan, Ranran Li, Rui Tian, Zhaojun Liu, Xiaoli Wang, Erzhen Chen, Tingting Pan, Hongping Qu","doi":"10.1186/s12950-023-00341-2","DOIUrl":"10.1186/s12950-023-00341-2","url":null,"abstract":"<p><strong>Background: </strong>Delayed neutrophil apoptosis during sepsis may impact neutrophil organ accumulation and tissue immune homeostasis. Elucidating the mechanisms underlying neutrophil apoptosis may help identify potential therapeutic targets. Glycolysis is critical to neutrophil activities during sepsis. However, the precise mechanisms through which glycolysis regulates neutrophil physiology remain under-explored, especially those involving the non-metabolic functions of glycolytic enzymes. In the present study, the impact of programmed death ligand-1 (PD-L1) on neutrophil apoptosis was explored. The regulatory effect of the glycolytic enzyme, pyruvate kinase M2 (PKM2), whose role in septic neutrophils remains unaddressed, on neutrophil PD-L1 expression was also explored.</p><p><strong>Methods: </strong>Peripheral blood neutrophils were isolated from patients with sepsis and healthy controls. PD-L1 and PKM2 levels were determined by flow cytometry and Western blotting, respectively. Dimethyl sulfoxide (DMSO)-differentiated HL-60 cells were stimulated with lipopolysaccharide (LPS) as an in vitro simulation of septic neutrophils. Cell apoptosis was assessed by annexin V/propidium iodide (annexin V/PI) staining, as well as determination of protein levels of cleaved caspase-3 and myeloid cell leukemia-1 (Mcl-1) by Western blotting. An in vivo model of sepsis was constructed by intraperitoneal injection of LPS (5 mg/kg) for 16 h. Pulmonary and hepatic neutrophil infiltration was assessed by flow cytometry or immunohistochemistry.</p><p><strong>Results: </strong>PD-L1 level was elevated on neutrophils under septic conditions. Administration of neutralizing antibodies against PD-L1 partially reversed the inhibitory effect of LPS on neutrophil apoptosis. Neutrophil infiltration into the lung and liver was also reduced in PD-L1^-/- mice 16 h after sepsis induction. PKM2 was upregulated in septic neutrophils and promoted neutrophil PD-L1 expression both in vitro and in vivo. In addition, PKM2 nuclear translocation was increased after LPS stimulation, which promoted PD-L1 expression by directly interacting with and activating signal transducer and activator of transcription 1 (STAT1). Inhibition of PKM2 activity or STAT1 activation also led to increased neutrophil apoptosis.</p><p><strong>Conclusion: </strong>In this study, a PKM2/STAT1-mediated upregulation of PD-L1 on neutrophils and the anti-apoptotic effect of upregulated PD-L1 on neutrophils during sepsis were identified, which may result in increased pulmonary and hepatic neutrophil accumulation. These findings suggest that PKM2 and PD-L1 could serve as potential therapeutic targets.</p>","PeriodicalId":56120,"journal":{"name":"Journal of Inflammation-London","volume":"20 1","pages":"16"},"PeriodicalIF":4.4,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10155438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9409824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}