Innate Immunity最新文献_第9页

Baicalin attenuates LPS-induced alveolar type II epithelial cell A549 injury by attenuation of the FSTL1 signaling pathway via increasing miR-200b-3p expression. 黄芩苷通过增加miR-200b-3p表达，减弱FSTL1信号通路，从而减轻lps诱导的肺泡II型上皮细胞A549损伤。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-05-01 Epub Date: 2021-05-18 DOI: 10.1177/17534259211013887

Xin-Ya Duan, Yang Sun, Zhu-Feng Zhao, Yao-Qing Shi, Xun-Yan Ma, Li Tao, Ming-Wei Liu

{"title":"Baicalin attenuates LPS-induced alveolar type II epithelial cell A549 injury by attenuation of the FSTL1 signaling pathway via increasing miR-200b-3p expression.","authors":"Xin-Ya Duan, Yang Sun, Zhu-Feng Zhao, Yao-Qing Shi, Xun-Yan Ma, Li Tao, Ming-Wei Liu","doi":"10.1177/17534259211013887","DOIUrl":"https://doi.org/10.1177/17534259211013887","url":null,"abstract":"In China, baicalin is the main active component of Scutellaria baicalensis, which has been used in the treatment of inflammation-related diseases, such as inflammation-induced acute lung injury. However, its specific mechanism remains unclear. This study examined the protective effect of baicalin on LPS-induced inflammation injury of alveolar epithelial cell line A549 and explored its protective mechanism. Compared with the LPS-induced group, the proliferation inhibition rates of alveolar type II epithelial cell line A549 intervened by different concentrations of baicalin decreased significantly, as did the levels of inflammatory factors IL-6, IL-1β, prostaglandin 2 and TNF-α in the supernatant. The expression levels of inflammatory proteins inducible NO synthase (iNOS), NF-κB65, phosphorylated ERK (p-ERK1/2), and phosphorylated c-Jun N-terminal kinase (p-JNK1) significantly decreased, as did the protein expression of follistatin-like protein 1 (FSTL1). In contrast, expression of miR-200b-3p significantly increased in a dose-dependent manner. These results suggested that baicalin could significantly inhibit the expression of inflammation-related proteins and improve LPS-induced inflammatory injury in alveolar type II epithelial cells. The mechanism may be related to the inhibition of ERK/JNK inflammatory pathway activation by increasing the expression of miR-200b-3p. Thus, FSTL1 is the regulatory target of miR-200b-3p.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 4","pages":"294-312"},"PeriodicalIF":3.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17534259211013887","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38992137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Anti-HMGB1 auto-Abs influence fatigue in patients with Crohn's disease. 抗hmgb1自身抗体对克罗恩病患者疲劳的影响

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-05-01 Epub Date: 2021-05-03 DOI: 10.1177/17534259211014252

Ingeborg Kvivik, Tore Grimstad, Grete Jonsson, Jan T Kvaløy, Roald Omdal

{"title":"Anti-HMGB1 auto-Abs influence fatigue in patients with Crohn's disease.","authors":"Ingeborg Kvivik, Tore Grimstad, Grete Jonsson, Jan T Kvaløy, Roald Omdal","doi":"10.1177/17534259211014252","DOIUrl":"https://doi.org/10.1177/17534259211014252","url":null,"abstract":"Fatigue is common in all chronic inflammatory and autoimmune diseases. A conceptual model for understanding the biological basis of fatigue describes it as being a part of the sickness behaviour response generated by pro-inflammatory cytokines and other mediators. We hypothesised that the pro-inflammatory high mobility group box 1 (HMGB1) protein is a fatigue-inducing molecule and that auto-Abs against HMGB1 reduce fatigue. We measured Abs against disulphide (ds) HMGB1 and fully reduced (fr) HMGB1 in plasma from 57 patients with Crohn's disease. Fatigue was rated using the fatigue visual analogue scale (fVAS) and disease activity with faecal calprotectin, C-reactive protein and the Simple Endoscopic Score for Crohn's disease. Multivariable regression models identified anti-dsHMGB1 and anti-frHMGB1 Abs as the strongest contributing factors for fVAS scores (B = -29.10 (P = 0.01), R2 = 0.17, and B = -17.77 (P = 0.01), R2 = 0.17, respectively). Results indicate that anti-HMGB1 auto-Abs alleviate fatigue possibly by down-regulating HMGB1-induced sickness behaviour.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 4","pages":"286-293"},"PeriodicalIF":3.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17534259211014252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38864353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Protective effects of recombinant 53-kDa protein of Trichinella spiralis on acute lung injury in mice via alleviating lung pyroptosis by promoting M2 macrophage polarization. 旋毛虫重组53-kDa蛋白通过促进M2巨噬细胞极化减轻肺焦亡对小鼠急性肺损伤的保护作用。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-05-01 Epub Date: 2021-05-20 DOI: 10.1177/17534259211013397

Ling-Yu Wei, An-Qi Jiang, Ren Jiang, Si-Ying Duan, Xue Xu, Ze-da-Zhong Su, Jia Xu

{"title":"Protective effects of recombinant 53-kDa protein of Trichinella spiralis on acute lung injury in mice via alleviating lung pyroptosis by promoting M2 macrophage polarization.","authors":"Ling-Yu Wei, An-Qi Jiang, Ren Jiang, Si-Ying Duan, Xue Xu, Ze-da-Zhong Su, Jia Xu","doi":"10.1177/17534259211013397","DOIUrl":"https://doi.org/10.1177/17534259211013397","url":null,"abstract":"Trichinella spiralis represents an effective treatment for autoimmune and inflammatory diseases. The effects of recombinant T. spiralis (TS) 53-kDa protein (rTsP53) on acute lung injury (ALI) remain unclear. Here, mice were divided randomly into a control group, LPS group, and rTsP53 + LPS group. ALI was induced in BALB/c mice by LPS (10 mg/kg) injected via the tail vein. rTsP53 (200 µl; 0.4 μg/μl) was injected subcutaneously three times at an interval of 5 d before inducing ALI in the rTsP53+LPS group. Lung pathological score, the ratio and markers of classic activated macrophages (M1) and alternatively activated macrophages (M2), cytokine profiles in alveolar lavage fluid, and pyroptosis protein expression in lung tissue were investigated. RTsP53 decreased lung pathological score. Furthermore, rTsP53 suppressed inflammation by increasing IL-4, IL-10, and IL-13. There was an increase in alveolar M2 macrophage numbers, with an increase in CD206 and arginase-1-positive cells and a decrease in alveolar M1 markers such as CD197 and iNOS. In addition, the polarization of M2 macrophages induced by rTsP53 treatment could alleviate ALI by suppressing lung pyroptosis. RTsP53 was identified as a potential agent for treating LPS-induced ALI via alleviating lung pyroptosis by promoting M2 macrophage polarization.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 4","pages":"313-323"},"PeriodicalIF":3.2,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17534259211013397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38930803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

A pilot study of an anti-endotoxin Ig-enriched bovine colostrum to prevent experimental sepsis. 富含抗内毒素 Ig 的牛初乳预防实验性败血症的试点研究。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 DOI: 10.1177/17534259211007538

Alan S Cross, Steven M Opal, John E Palardy, Surekha Shridhar, Scott M Baliban, Alison J Scott, Abdullah B Chahin, Robert K Ernst

{"title":"A pilot study of an anti-endotoxin Ig-enriched bovine colostrum to prevent experimental sepsis.","authors":"Alan S Cross, Steven M Opal, John E Palardy, Surekha Shridhar, Scott M Baliban, Alison J Scott, Abdullah B Chahin, Robert K Ernst","doi":"10.1177/17534259211007538","DOIUrl":"10.1177/17534259211007538","url":null,"abstract":"Despite the dramatic increase in antimicrobial resistance, there is a dearth of antibiotics in development and few pharmaceutical companies working in the field. Further, any new antibiotics are likely to have a short shelf life. Ab-based interventions offer alternatives that are not likely to be circumvented by the widely prevalent antibiotic resistance genes. Bovine colostrum (BC)-the first milk after parturition, rich in nutrients and immune components-promotes gut integrity and modulates the gut microbiome. We developed a hyperimmune BC (HBC) enriched in Abs to a highly conserved LOS core region of Gram-negative bacteria by immunizing pregnant cows with a vaccine comprised of detoxified LOS from Escherichia coli O111 Rc (J5) mutant non-covalently complexed to group B meningococcal outer membrane protein (J5dLOS/OMP). This vaccine generated robust levels of anti-J5 LOS Ab in the colostrum. When given orally to neutropenic rats challenged orally with Pseudomonas aeruginosa, administration of HBC improved survival compared to non-immune rats, while both BC preparations improved survival compared to PBS controls. Elevated circulating endotoxin levels correlated with mortality. HBC and to a lesser extent non-immune BC reduced bacterial burden from the liver, lung, and spleen. We conclude that HBC and to a lesser extent BC may be effective supplements that improve outcome from lethal gut-derived disseminated infection and may reduce transmission of Gram-negative bacilli from the gastrointestinal tract.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 3","pages":"266-274"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fa/a9/10.1177_17534259211007538.PMC8054147.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38797577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anti-nociceptive effect of Portulaca oleracea L. ethanol extracts attenuated zymosan-induced mouse joint inflammation via inhibition of Nrf2 expression. 马齿苋乙醇提取物通过抑制Nrf2的表达来减轻酵素诱导的小鼠关节炎症的抗伤害作用。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 Epub Date: 2021-02-20 DOI: 10.1177/1753425921994190

Yunwu He, Hui Long, Cong Zou, Wuzhou Yang, Liping Jiang, Zhenping Xiao, Qing Li, Shiyin Long

{"title":"Anti-nociceptive effect of Portulaca oleracea L. ethanol extracts attenuated zymosan-induced mouse joint inflammation via inhibition of Nrf2 expression.","authors":"Yunwu He, Hui Long, Cong Zou, Wuzhou Yang, Liping Jiang, Zhenping Xiao, Qing Li, Shiyin Long","doi":"10.1177/1753425921994190","DOIUrl":"https://doi.org/10.1177/1753425921994190","url":null,"abstract":"The aim of this study was to explore the effects of ethanol extracts from Portulaca oleracea L. (ePO) on joint inflammation and to explain the underlying mechanisms. A joint inflammation mouse model was constructed by injecting zymosan, and the Von Frey method was employed and the joint thickness measured. The numbers of leukocytes, neutrophils, and monocytes were counted in the joint cavity and the infiltration of inflammatory cells was assessed by joint histopathological analysis. The mRNA levels of inflammatory cytokines were determined by quantitative RT-PCR and their secretion levels were determined by specific ELISAs. Pre-treatment with ePO inhibited articular mechanical hyperalgesia and edema and ameliorated the recruitment of mononuclear neutrophils and leukocytes. In addition, pre-treatment with ePO improved pathological alternations in the joint tissues by reducing the number of inflammatory cells. Pre-treatment with ePO regulated the nuclear factor erythroid 2-related factor 2 (Nrf2)-related proteins and thereby inhibited oxidative stress. In addition, ePO inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome-related genes (NLRP3, ASC, pro-caspase-1 and pro-IL-1ß), modulated inflammatory cytokines and the activation of NF-κB. ePO attenuated zymosan-induced joint inflammation by regulating oxidative stress, NLRP3 inflammasome, and NF-κB.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 3","pages":"230-239"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425921994190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25389351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Circulating cell-free DNA, peripheral lymphocyte subsets alterations and neutrophil lymphocyte ratio in assessment of COVID-19 severity. 循环游离DNA、外周血淋巴细胞亚群改变和中性粒细胞比例在评估COVID-19严重程度中的作用。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 Epub Date: 2021-03-01 DOI: 10.1177/1753425921995577

Reham Hammad, Mona Abd El Rahman Eldosoky, Shaimaa Hani Fouad, Abdelaleem Elgendy, Amany M Tawfeik, Mohamed Alboraie, Mariam Fathy Abdelmaksoud

{"title":"Circulating cell-free DNA, peripheral lymphocyte subsets alterations and neutrophil lymphocyte ratio in assessment of COVID-19 severity.","authors":"Reham Hammad, Mona Abd El Rahman Eldosoky, Shaimaa Hani Fouad, Abdelaleem Elgendy, Amany M Tawfeik, Mohamed Alboraie, Mariam Fathy Abdelmaksoud","doi":"10.1177/1753425921995577","DOIUrl":"https://doi.org/10.1177/1753425921995577","url":null,"abstract":"Cell destruction results in plasma accumulation of cell-free DNA (cfDNA). Dynamic changes in circulating lymphocytes are features of COVID-19. We aimed to investigate if cfDNA level can serve in stratification of COVID-19 patients, and if cfDNA level is associated with alterations in lymphocyte subsets and neutrophil-to-lymphocyte ratio (NLR). This cross-sectional comparative study enrolled 64 SARS-CoV-2-positive patients. Patients were subdivided to severe and non-severe groups. Plasma cfDNA concentration was determined by real-time quantitative PCR. Lymphocyte subsets were assessed by flow cytometry. There was significant increase in cfDNA among severe cases when compared with non-severe cases. cfDNA showed positive correlation with NLR and inverse correlation with T cell percentage. cfDNA positively correlated with ferritin and C-reactive protein. The output data of performed ROC curves to differentiate severe from non-severe cases revealed that cfDNA at cut-off ≥17.31 ng/µl and AUC of 0.96 yielded (93%) sensitivity and (73%) specificity. In summary, excessive release of cfDNA can serve as sensitive COVID-19 severity predictor. There is an association between cfDNA up-regulation and NLR up-regulation and T cell percentage down-regulation. cfDNA level can be used in stratification and personalized monitoring strategies in COVID-19 patients.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 3","pages":"240-250"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425921995577","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25417613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia. 流感嗜血杆菌引起人支气管上皮细胞的转分化。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 Epub Date: 2021-03-01 DOI: 10.1177/1753425921994906

Michael Glöckner, Sebastian Marwitz, Kristina Rohmann, Henrik Watz, Dörte Nitschkowski, Jan Rupp, Klaus Dalhoff, Torsten Goldmann, Daniel Drömann

{"title":"Haemophilus influenzae causes cellular trans-differentiation in human bronchial epithelia.","authors":"Michael Glöckner, Sebastian Marwitz, Kristina Rohmann, Henrik Watz, Dörte Nitschkowski, Jan Rupp, Klaus Dalhoff, Torsten Goldmann, Daniel Drömann","doi":"10.1177/1753425921994906","DOIUrl":"https://doi.org/10.1177/1753425921994906","url":null,"abstract":"Non-typeable Haemophilus influenzae (NTHi) is the most common respiratory pathogen in patients with chronic obstructive disease. Limited data is available investigating the impact of NTHi infections on cellular re-differentiation processes in the bronchial mucosa. The aim of this study was to assess the effects of stimulation with NTHi on the bronchial epithelium regarding cellular re-differentiation processes using primary bronchial epithelial cells harvested from infection-free patients undergoing bronchoscopy. The cells were then cultivated using an air-liquid interface and stimulated with NTHi and TGF-β. Markers of epithelial and mesenchymal cells were analyzed using immunofluorescence, Western blot and qRT-PCR. Stimulation with both NTHi and TGF-ß led to a marked increase in the expression of the mesenchymal marker vimentin, while E-cadherin as an epithelial marker maintained a stable expression throughout the experiments. Furthermore, expression of collagen 4 and the matrix-metallopeptidases 2 and 9 were increased after stimulation, while the expression of tissue inhibitors of metallopeptidases was not affected by pathogen stimulation. In this study we show a direct pathogen-induced trans-differentiation of primary bronchial epithelial cells resulting in a co-localization of epithelial and mesenchymal markers and an up-regulation of extracellular matrix components.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 3","pages":"251-259"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425921994906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25423937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Matrix metalloproteinase-9 -1562 C/T polymorphism is associated with the risk of sepsis in a Chinese population: A retrospective study. 基质金属蛋白酶-9 -1562 C/T多态性与中国人群败血症风险相关:一项回顾性研究

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 Epub Date: 2021-02-16 DOI: 10.1177/1753425921992414

Cuijuan Zheng, Jiayu Wang, Shouxiang Xie

{"title":"Matrix metalloproteinase-9 -1562 C/T polymorphism is associated with the risk of sepsis in a Chinese population: A retrospective study.","authors":"Cuijuan Zheng, Jiayu Wang, Shouxiang Xie","doi":"10.1177/1753425921992414","DOIUrl":"https://doi.org/10.1177/1753425921992414","url":null,"abstract":"Matrix metalloproteinase-9 (MMP-9) has been shown to participate in the pathogenesis of sepsis. In this study, we recruited 312 sepsis patients and 413 controls to explore the relationship between sepsis risk and the MMP-9 -1562 C/T polymorphism in Han Chinese. The PCR restriction fragment length polymorphism method was used for genotyping. Our data indicated that the MMP-9 -1562 C/T polymorphism was related with the risk of sepsis (CT vs. CC: P = 0.033, odds ratio (OR) = 1.45, 95% confidence interval (CI) 1.03-2.05; TT+CT vs. CC: P = 0.019, OR = 1.49, 95% CI 1.07-2.07). Stratified analyses demonstrated that this effect was more evident in smokers, drinkers, females and overweight individuals. Furthermore, cross-over analyses suggested that the combined effect of smoking and CT genotype of -1562 C/T polymorphism contributed to the risk of sepsis. In addition, MMP-9 serum levels were significantly lower in sepsis patients than in controls. The MMP-9 -1562 C/T polymorphism was significantly associated with decreased MMP-9 serum levels. Lastly, we observed that this polymorphism was connected to the mortality of sepsis. In conclusion, the interaction between the MMP-9 -1562 C/T polymorphism and smoking correlated with the risk of sepsis in Han Chinese. This polymorphism may serve as a diagnostic marker for sepsis patients.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 3","pages":"260-265"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425921992414","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25374398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages. 合成糖脂基TLR4拮抗剂负向调节人巨噬细胞中trf依赖的TLR4信号传导。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 DOI: 10.1177/17534259211005840

Charys Palmer, Fabio A Facchini, Richard Po Jones, Frank Neumann, Francesco Peri, Grisha Pirianov

{"title":"Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages.","authors":"Charys Palmer, Fabio A Facchini, Richard Po Jones, Frank Neumann, Francesco Peri, Grisha Pirianov","doi":"10.1177/17534259211005840","DOIUrl":"https://doi.org/10.1177/17534259211005840","url":null,"abstract":"TLRs, including TLR4, play a crucial role in inflammatory-based diseases, and TLR4 has been identified as a therapeutic target for pharmacological intervention. In previous studies, we investigated the potential of FP7, a novel synthetic glycolipid active as a TLR4 antagonist, to inhibit haematopoietic and non-haematopoietic MyD88-dependent TLR4 pro-inflammatory signalling. The main aim of this study was to investigate the action of FP7 and its derivative FP12 on MyD88-independent TLR4 signalling in THP-1 derived macrophages. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 and FP12 on TRIF-dependent TLR4 functional activity in response to LPS and other endogenous TLR4 ligands in THP-1 macrophages. A different kinetic in the inhibition of endotoxin-driven TBK1, IRF3 and STAT1 phosphorylation was observed using different LPS chemotypes. Following activation of TLR4 by LPS, data revealed that FP7 and FP12 inhibited TBK1, IRF3 and STAT1 phosphorylation which was associated with down-regulation IFN-β and IP-10. Specific blockage of the IFN type one receptor showed that these novel molecules inhibited TRIF-dependent TLR4 signalling via IFN-β pathways. These results add novel information on the mechanism of action of monosaccharide FP derivatives. The inhibition of the TRIF-dependent pathway in human macrophages suggests potential therapeutic uses for these novel TLR4 antagonists in pharmacological interventions on inflammatory diseases.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 3","pages":"275-284"},"PeriodicalIF":3.2,"publicationDate":"2021-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/17534259211005840","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38797575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Human NK cells: From development to effector functions. 人类 NK 细胞：从发育到效应功能

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-04-01 Epub Date: 2021-03-24 DOI: 10.1177/17534259211001512

Arosh Shavinda Perera Molligoda Arachchige

引用次数: 0