{"title":"通过触发髓系细胞 1 上表达的受体激活收费样受体 4/ 核因子-kappa B 信号,促进肺泡巨噬细胞 M1 极化并加重脓毒性急性肺损伤","authors":"Qingwu Liao, Xiaojuan Su, Zhengang Tao, Zheng Li, Huilin Wang, Ying Yuan","doi":"10.1002/jgm.3650","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Septic acute lung injury (ALI) is a life-threatening condition commonly occurring in the intensive care unit. Inflammation is considered as the basic pathological response of septic ALI. Triggering receptor expressed on myeloid cells 1 (TREM1) is a member of the immunoglobulin superfamily receptors that regulates the inflammatory response. However, the role of TREM1 in septic ALI has not yet been reported.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Cell viability was tested using the MTT assay. TdT-mediated dUTP nick end labeling assay and flow cytometry were used for apoptosis. The level of protein was detected using western blot analysis. The levels of tumor necrosis factor-<i>α</i> and interleukin-1<i>β</i> were assessed using enzyme-linked immunosorbent assay. The lactate dehydrogenase content was assessed using the assay kit. Myeloperoxidase activity was determined using an assay. Histology of lung tissue was further analyzed through hematoxylin–eosin staining.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We found that TREM1 knockdown by transfection with si-TREM1 inhibited lipopolysaccharide (LPS)-induced cell apoptosis of alveolar macrophage cell line MH-S. The LPS stimulation caused M1 polarization of MH-S cells, which could be reversed by TREM1 knockdown. <i>In vivo</i> assays proved that si-TREM1 injection improved lung injury and inflammation of cecal ligation and puncture-induced ALI in mice. In addition, TREM1 knockdown suppressed the activation of toll-like receptor 4/nuclear factor-kappa B signaling, implying the involvement of TLR4 in the effects of TREM1 in response to LPS stimulation.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>This study examined the proinflammatory role of TREM1 in septic ALI and its regulatory effect on alveolar macrophage polarization. These results suggest that TREM1 could potentially serve as a therapeutic target in the prevention and treatment of ALI.</p>\n </section>\n </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Activation of toll-like receptor 4/nuclear factor-kappa B signaling by triggering a receptor expressed on myeloid cells 1 promotes alveolar macrophage M1 polarization and exacerbates septic acute lung injury\",\"authors\":\"Qingwu Liao, Xiaojuan Su, Zhengang Tao, Zheng Li, Huilin Wang, Ying Yuan\",\"doi\":\"10.1002/jgm.3650\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Septic acute lung injury (ALI) is a life-threatening condition commonly occurring in the intensive care unit. Inflammation is considered as the basic pathological response of septic ALI. Triggering receptor expressed on myeloid cells 1 (TREM1) is a member of the immunoglobulin superfamily receptors that regulates the inflammatory response. However, the role of TREM1 in septic ALI has not yet been reported.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Cell viability was tested using the MTT assay. TdT-mediated dUTP nick end labeling assay and flow cytometry were used for apoptosis. The level of protein was detected using western blot analysis. The levels of tumor necrosis factor-<i>α</i> and interleukin-1<i>β</i> were assessed using enzyme-linked immunosorbent assay. The lactate dehydrogenase content was assessed using the assay kit. Myeloperoxidase activity was determined using an assay. Histology of lung tissue was further analyzed through hematoxylin–eosin staining.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>We found that TREM1 knockdown by transfection with si-TREM1 inhibited lipopolysaccharide (LPS)-induced cell apoptosis of alveolar macrophage cell line MH-S. The LPS stimulation caused M1 polarization of MH-S cells, which could be reversed by TREM1 knockdown. <i>In vivo</i> assays proved that si-TREM1 injection improved lung injury and inflammation of cecal ligation and puncture-induced ALI in mice. In addition, TREM1 knockdown suppressed the activation of toll-like receptor 4/nuclear factor-kappa B signaling, implying the involvement of TLR4 in the effects of TREM1 in response to LPS stimulation.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>This study examined the proinflammatory role of TREM1 in septic ALI and its regulatory effect on alveolar macrophage polarization. These results suggest that TREM1 could potentially serve as a therapeutic target in the prevention and treatment of ALI.</p>\\n </section>\\n </div>\",\"PeriodicalId\":56122,\"journal\":{\"name\":\"Journal of Gene Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2023-12-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Gene Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jgm.3650\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gene Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jgm.3650","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
化脓性急性肺损伤(ALI)是重症监护室中常见的一种危及生命的疾病。炎症被认为是化脓性急性肺损伤的基本病理反应。髓系细胞上表达的触发受体 1(TREM1)是免疫球蛋白超家族受体的成员之一,可调节炎症反应。然而,TREM1 在脓毒症 ALI 中的作用尚未见报道。
Activation of toll-like receptor 4/nuclear factor-kappa B signaling by triggering a receptor expressed on myeloid cells 1 promotes alveolar macrophage M1 polarization and exacerbates septic acute lung injury
Background
Septic acute lung injury (ALI) is a life-threatening condition commonly occurring in the intensive care unit. Inflammation is considered as the basic pathological response of septic ALI. Triggering receptor expressed on myeloid cells 1 (TREM1) is a member of the immunoglobulin superfamily receptors that regulates the inflammatory response. However, the role of TREM1 in septic ALI has not yet been reported.
Methods
Cell viability was tested using the MTT assay. TdT-mediated dUTP nick end labeling assay and flow cytometry were used for apoptosis. The level of protein was detected using western blot analysis. The levels of tumor necrosis factor-α and interleukin-1β were assessed using enzyme-linked immunosorbent assay. The lactate dehydrogenase content was assessed using the assay kit. Myeloperoxidase activity was determined using an assay. Histology of lung tissue was further analyzed through hematoxylin–eosin staining.
Results
We found that TREM1 knockdown by transfection with si-TREM1 inhibited lipopolysaccharide (LPS)-induced cell apoptosis of alveolar macrophage cell line MH-S. The LPS stimulation caused M1 polarization of MH-S cells, which could be reversed by TREM1 knockdown. In vivo assays proved that si-TREM1 injection improved lung injury and inflammation of cecal ligation and puncture-induced ALI in mice. In addition, TREM1 knockdown suppressed the activation of toll-like receptor 4/nuclear factor-kappa B signaling, implying the involvement of TLR4 in the effects of TREM1 in response to LPS stimulation.
Conclusions
This study examined the proinflammatory role of TREM1 in septic ALI and its regulatory effect on alveolar macrophage polarization. These results suggest that TREM1 could potentially serve as a therapeutic target in the prevention and treatment of ALI.
期刊介绍:
The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies.
Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials.
Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.