Innate Immunity最新文献_第8页

Circ_0026579 alleviates LPS-induced WI-38 cells inflammation injury in infantile pneumonia. Circ_0026579减轻lps诱导的婴儿肺炎WI-38细胞炎症损伤。

IF 3.2 4区医学

Innate Immunity Pub Date : 2022-01-01 DOI: 10.1177/17534259211069104

Yang Yu, Tingting Yang, Zhaozheng Ding, Yuan Cao

{"title":"Circ_0026579 alleviates LPS-induced WI-38 cells inflammation injury in infantile pneumonia.","authors":"Yang Yu, Tingting Yang, Zhaozheng Ding, Yuan Cao","doi":"10.1177/17534259211069104","DOIUrl":"https://doi.org/10.1177/17534259211069104","url":null,"abstract":"Circular RNA (circRNA) represents an important regulator in infantile pneumonia progression. To clarify the role of circ_0026579 in this disease, LPS was used to treat WI-38 cells to mimic inflammation injury. The levels of inflammatory factors were determined by ELISA assay. Cell proliferation and apoptosis were measured by MTT assay, EdU staining and flow cytometry. The protein levels of cyclinD1, cleaved-caspase-3 and insulin-like growth factor 2 (IGF2) were examined using Western blot analysis. Cell oxidative stress was assessed by detecting MDA level and SOD activity. The expression of circ_0026579, miR-24-3p and IGF2 were analyzed using quantitative real-time PCR, and the interaction between miR-24-3p and circ_0026579 or IGF2 was confirmed by dual-luciferase reporter assay and RIP assay. LPS induced inflammation in WI-38 cells. Circ_0026579 expression was promoted in LPS-induced WI-38 cells, and its knockdown alleviated LPS-induced WI-38 cells inflammation. MiR-24-3p was sponged by circ_0026579, and its expression was reduced by LPS. MiR-24-3p inhibitor reversed the regulation of circ_0026579 knockdown on LPS-induced WI-38 cells inflammation. IGF2 was targeted by miR-24-3p, and its expression could be enhanced by LPS. MiR-24-3p relieved the inflammation of WI-38 cells which could be abolished by IGF2 overexpression. Circ_0026579 positively regulated IGF2 expression through sponging miR-24-3p. Circ_0026579 knockdown alleviated LPS-induced WI-38 cells inflammation by miR-24-3p/IGF2 axis, suggesting that circ_0026579 might contribute to infantile pneumonia progression.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"28 1","pages":"37-48"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f1/d6/10.1177_17534259211069104.PMC8841632.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782420","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

Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis. 托珠单抗治疗的重症SARS-CoV-2患者的延迟炎症减轻与死亡率相关:一项回顾性匹配队列分析

IF 3.2 4区医学

Innate Immunity Pub Date : 2022-01-01 Epub Date: 2022-01-28 DOI: 10.1177/17534259211064602

Tomas Urbina, Jean-Rémi Lavillegrand, Marc Garnier, Arsene Mekinian, Jerome Pacanowski, Nathalie Mario, Guillaume Dumas, Geoffroy Hariri, Antoine Pilon, Lucie Darrivère, Muriel Fartoukh, Bertrand Guidet, Eric Maury, Judith Leblanc, Yannick Chantran, Olivier Fain, Karine Lacombe, Guillaume Voiriot, Hafid Ait-Oufella

{"title":"Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis.","authors":"Tomas Urbina, Jean-Rémi Lavillegrand, Marc Garnier, Arsene Mekinian, Jerome Pacanowski, Nathalie Mario, Guillaume Dumas, Geoffroy Hariri, Antoine Pilon, Lucie Darrivère, Muriel Fartoukh, Bertrand Guidet, Eric Maury, Judith Leblanc, Yannick Chantran, Olivier Fain, Karine Lacombe, Guillaume Voiriot, Hafid Ait-Oufella","doi":"10.1177/17534259211064602","DOIUrl":"https://doi.org/10.1177/17534259211064602","url":null,"abstract":"Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"28 1","pages":"3-10"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/99/10.1177_17534259211064602.PMC8841634.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39743896","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: 1

Early kinetics of calprotectin in plasma following inguinal hernia surgery. 腹股沟疝手术后血浆钙保护蛋白的早期动力学。

IF 3.2 4区医学

Innate Immunity Pub Date : 2022-01-01 Epub Date: 2022-02-01 DOI: 10.1177/17534259211069635

Kristina Sejersen, Aleksandra Havelka, Pearl Sanchez Salas, Anders Larsson

{"title":"Early kinetics of calprotectin in plasma following inguinal hernia surgery.","authors":"Kristina Sejersen, Aleksandra Havelka, Pearl Sanchez Salas, Anders Larsson","doi":"10.1177/17534259211069635","DOIUrl":"https://doi.org/10.1177/17534259211069635","url":null,"abstract":"Calprotectin is one of the most abundant proteins of neutrophil granulocytes. It is released upon neutrophil activation and is considered a sensitive and clinically useful marker for neutrophil-mediated inflammation, including bacterial infections. However, early kinetics of calprotectin activation following inflammatory activation has hitherto been unknown. The aim of the present study was to determine the early phase of the kinetics of calprotectin, in comparison with the inflammatory markers CRP, IL-6, TNF-α, and procalcitonin, in plasma following a standardized temporary mild inflammatory response, using uncomplicated inguinal hernia surgery as a model. The study cohort consisted of 17 adult patients (15 male and 2 female) undergoing elective surgery for hernia. Values of calprotectin increased significantly at 2 h following surgery, and continued to increase to reach the highest level at 24-36 h after surgery, values still not exceeding upper normal reference level. This contrasts to IL-6 and CRP, for which an elevation was found first later, 4 h and 24-36 h post-surgery, respectively, for IL-6, and CRP. No significant increase was seen for TNF-α, or procalcitonin. The data demonstrate a very rapid and significant but modest increase in calprotectin following induction of mild inflammation, supporting that calprotectin can be useful for early detection of inflammatory response.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"28 1","pages":"49-54"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8841635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39739195","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

Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis. 三七皂苷R1通过调节miR-128-2-5p/Tollip信号通路对重症急性胰腺炎大鼠急性肺损伤的保护作用

IF 3.2 4区医学

Innate Immunity Pub Date : 2022-01-01 DOI: 10.1177/17534259211068744

Ju He, Ming-Wei Liu, Zhi-Yi Wang, Rong-Jie Shi

{"title":"Protective effects of the notoginsenoside R1 on acute lung injury by regulating the miR-128-2-5p/Tollip signaling pathway in rats with severe acute pancreatitis.","authors":"Ju He, Ming-Wei Liu, Zhi-Yi Wang, Rong-Jie Shi","doi":"10.1177/17534259211068744","DOIUrl":"https://doi.org/10.1177/17534259211068744","url":null,"abstract":"Notoginsenoside R1 (NG-R1), the extract and the main ingredient of Panax notoginseng, has anti-inflammatory effects and can be used in treating acute lung injury (ALI). In this study, we explored the pulmonary protective effect and the underlying mechanism of the NG-R1 on rats with ALI induced by severe acute pancreatitis (SAP). MiR-128-2-5p, ERK1, Tollip, HMGB1, TLR4, IκB, and NF-κB mRNA expression levels were measured using real-time qPCR, and TLR4, Tollip, HMGB1, IRAK1, MyD88, ERK1, NF-κB65, and P-IκB-α protein expression levels using Western blot. The NF-κB and the TLR4 activities were determined using immunohistochemistry, and TNF-α, IL-6, IL-1β, and ICAM-1 levels in the bronchoalveolar lavage fluid (BALF) using ELISA. Lung histopathological changes were observed in each group. NG-R1 treatment reduced miR-128-2-5p expression in the lung tissue, increased Tollip expression, inhibited HMGB1, TLR4, TRAF6, IRAK1, MyD88, NF-κB65, and p-IκB-α expression levels, suppressed NF-κB65 and the TLR4 expression levels, reduced MPO activity, reduced TNF-α, IL-1β, IL-6, and ICAM-1 levels in BALF, and alleviated SAP-induced ALI. NG-R1 can attenuate SAP-induced ALI. The mechanism of action may be due to a decreased expression of miR-128-2-5p, increased activity of the Tollip signaling pathway, decreased activity of HMGB1/TLR4 and ERK1 signaling pathways, and decreased inflammatory response to SAP-induced ALI. Tollip was the regulatory target of miR-128-2-5p.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"28 1","pages":"19-36"},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/e4/10.1177_17534259211068744.PMC8841636.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39782421","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: 5

Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB. 佛手柑素通过诱导SIRT1、抑制NF-κB减轻lps诱导的急性肺损伤。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-10-01 Epub Date: 2021-11-23 DOI: 10.1177/17534259211062553

Ning An, Tao Yang, Xiao-Xia Zhang, Mei-Xia Xu

{"title":"Bergamottin alleviates LPS-induced acute lung injury by inducing SIRT1 and suppressing NF-κB.","authors":"Ning An, Tao Yang, Xiao-Xia Zhang, Mei-Xia Xu","doi":"10.1177/17534259211062553","DOIUrl":"https://doi.org/10.1177/17534259211062553","url":null,"abstract":"Acute lung injury (ALI) is associated with a high mortality due to inflammatory cell infiltration and lung edema. The development of ALI commonly involves the activation of NF-κB. Since bergamottin is a natural furanocoumarin showing the ability to inhibit the activation of NF-κB, in this study we aimed to determine the effect of bergamottin on ALI. RAW264.7 mouse macrophages were pre-treated with bergamottin and then stimulated with LPS. Macrophage inflammatory responses were examined. Bergamottin (50 mg/kg body mass) was intraperitoneally administrated to mice 12 h before injection of LPS, and the effect of bergamottin on LPS-induced ALI was evaluated. Our results showed that LPS exposure led to increased production of TNF-α, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which was impaired by bergamottin pre-treatment. In vivo studies confirmed that bergamottin pre-treatment suppressed LPS-induced lung inflammation and edema and reduced the levels of pro-inflammatory cytokines in lung tissues and bronchoalveolar lavage fluids. Mechanistically, bergamottin blocked LPS-induced activation of NF-κB signaling in lung tissues. Additionally, bergamottin treatment reduced NF-κB p65 protein acetylation, which was coupled with induction of SIRT1 expression. In conclusion, our results reveal the anti-inflammatory property of bergamottin in preventing ALI. Induction of SIRT1 and inhibition of NF-κB underlies the anti-inflammatory activity of bergamottin.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 7-8","pages":"543-552"},"PeriodicalIF":3.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/f6/10.1177_17534259211062553.PMC8762093.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39650407","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: 6

Enteral nutrition ameliorates the symptoms of Crohn's disease in mice via activating special pro-resolving mediators through innate lymphoid cells. 肠内营养通过先天淋巴样细胞激活特殊的促溶解介质，改善小鼠克罗恩病的症状。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-10-01 Epub Date: 2021-11-18 DOI: 10.1177/17534259211057038

Di Zhao, Bo Yang, Chen Ye, Shaoyi Zhang, Xiaoqiong Lv, Qiyi Chen

引用次数: 3

TLRs in COVID-19: How they drive immunopathology and the rationale for modulation. tlr在COVID-19中的作用:它们如何驱动免疫病理以及调节的基本原理。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-10-01 Epub Date: 2021-11-20 DOI: 10.1177/17534259211051364

F Linzee Mabrey, Eric D Morrell, Mark M Wurfel

引用次数: 24

Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways. 黄脾醇D通过TLR4-MAPKs/NF-κB信号通路抑制氧化应激、炎症和凋亡，保护小鼠免受lps诱导的急性肺损伤。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-10-01 Epub Date: 2021-11-20 DOI: 10.1177/17534259211051069

Qinqin Zhang, Aozi Feng, Mengnan Zeng, Beibei Zhang, Jingya Shi, Yaxin Lv, Bing Cao, Chenxin Zhao, Mengya Wang, Yifan Ding, Xiaoke Zheng

{"title":"Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways.","authors":"Qinqin Zhang, Aozi Feng, Mengnan Zeng, Beibei Zhang, Jingya Shi, Yaxin Lv, Bing Cao, Chenxin Zhao, Mengya Wang, Yifan Ding, Xiaoke Zheng","doi":"10.1177/17534259211051069","DOIUrl":"10.1177/17534259211051069","url":null,"abstract":"This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1β, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1β, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1β in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1β, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 7-8","pages":"514-524"},"PeriodicalIF":3.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/89/10.1177_17534259211051069.PMC8762090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39645610","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: 10

Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet. 循环先天性淋巴细胞亚型和致动脉粥样硬化高脂饮食后细胞因子谱的改变。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-10-01 Epub Date: 2021-11-17 DOI: 10.1177/17534259211053634

Vuyolwethu Mxinwa, Phiwayinkosi V Dludla, Tawanda M Nyambuya, Bongani B Nkambule

{"title":"Circulating innate lymphoid cell subtypes and altered cytokine profiles following an atherogenic high-fat diet.","authors":"Vuyolwethu Mxinwa, Phiwayinkosi V Dludla, Tawanda M Nyambuya, Bongani B Nkambule","doi":"10.1177/17534259211053634","DOIUrl":"10.1177/17534259211053634","url":null,"abstract":"Impaired Glc tolerance and hyperinsulinemia are a hallmark of type 2 diabetes (T2D) and are associated with an altered innate and adaptive immune response. In this study, we used a high-fat diet (HFD)-induced model of pre-diabetes to explore the pathological implications of altered innate lymphoid cell (ILC) profiles in a state of impaired Glc tolerance. Sixteen male C57BL/6 mice were randomized to receive two experimental diets (n = 8 per group), low-fat (LFD), and HFD for 8-13 wk. We evaluated the levels of circulating innate lymphoid cells and their respective cytokines following HFD-feeding. The HFD group had impaired Glc tolerance, elevated insulin levels, and increased total cholesterol levels. Notably, the levels of circulating ILC1s were elevated following 13 wk of HFD-feeding. Moreover, the levels of TNF-α were decreased, but there were no changes in IFN-γ levels. Lastly, the levels of circulating ILC2s and ILC3s were comparable between the HFD and LFD group. The findings demonstrated that short-term HFD-feeding increases postprandial blood Glc, total cholesterol and insulin levels. However, the metabolic changes did not alter ILC2 and ILC3 levels and their respective cytokine profiles.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 7-8","pages":"525-532"},"PeriodicalIF":3.2,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/1e/10.1177_17534259211053634.PMC8762092.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39631154","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

Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88. Lys694Arg多态性通过干扰TLR4与MyD88的募集而导致对LPS的迟钝反应。

IF 3.2 4区医学

Innate Immunity Pub Date : 2021-08-01 Epub Date: 2020-06-08 DOI: 10.1177/1753425920927479

Yajie Yang, Yan Hu, Yile Zhou, Tao Liang, Haihong Tang, Huihui Ju, Qiqing Shi, Hao Fang

{"title":"Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88.","authors":"Yajie Yang, Yan Hu, Yile Zhou, Tao Liang, Haihong Tang, Huihui Ju, Qiqing Shi, Hao Fang","doi":"10.1177/1753425920927479","DOIUrl":"https://doi.org/10.1177/1753425920927479","url":null,"abstract":"TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":"27 6","pages":"483-492"},"PeriodicalIF":3.2,"publicationDate":"2021-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425920927479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38027226","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