Innate Immunity最新文献

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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 <i>Portulaca oleracea</i> L. ethanol extracts attenuated zymosan-induced mouse joint inflammation via inhibition of Nrf2 expression.","authors":"Yunwu He,&nbsp;Hui Long,&nbsp;Cong Zou,&nbsp;Wuzhou Yang,&nbsp;Liping Jiang,&nbsp;Zhenping Xiao,&nbsp;Qing Li,&nbsp;Shiyin Long","doi":"10.1177/1753425921994190","DOIUrl":"https://doi.org/10.1177/1753425921994190","url":null,"abstract":"<p><p>The aim of this study was to explore the effects of ethanol extracts from <i>Portulaca oleracea</i> 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.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"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,&nbsp;Mona Abd El Rahman Eldosoky,&nbsp;Shaimaa Hani Fouad,&nbsp;Abdelaleem Elgendy,&nbsp;Amany M Tawfeik,&nbsp;Mohamed Alboraie,&nbsp;Mariam Fathy Abdelmaksoud","doi":"10.1177/1753425921995577","DOIUrl":"https://doi.org/10.1177/1753425921995577","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"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":"<i>Haemophilus influenza</i>e causes cellular trans-differentiation in human bronchial epithelia.","authors":"Michael Glöckner,&nbsp;Sebastian Marwitz,&nbsp;Kristina Rohmann,&nbsp;Henrik Watz,&nbsp;Dörte Nitschkowski,&nbsp;Jan Rupp,&nbsp;Klaus Dalhoff,&nbsp;Torsten Goldmann,&nbsp;Daniel Drömann","doi":"10.1177/1753425921994906","DOIUrl":"https://doi.org/10.1177/1753425921994906","url":null,"abstract":"<p><p>Non-typeable <i>Haemophilus influenzae</i> (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.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"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,&nbsp;Jiayu Wang,&nbsp;Shouxiang Xie","doi":"10.1177/1753425921992414","DOIUrl":"https://doi.org/10.1177/1753425921992414","url":null,"abstract":"<p><p>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: <i>P</i> = 0.033, odds ratio (OR) = 1.45, 95% confidence interval (CI) 1.03-2.05; TT+CT vs. CC: <i>P</i> = 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.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"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,&nbsp;Fabio A Facchini,&nbsp;Richard Po Jones,&nbsp;Frank Neumann,&nbsp;Francesco Peri,&nbsp;Grisha Pirianov","doi":"10.1177/17534259211005840","DOIUrl":"https://doi.org/10.1177/17534259211005840","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"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
{"title":"Human NK cells: From development to effector functions.","authors":"Arosh Shavinda Perera Molligoda Arachchige","doi":"10.1177/17534259211001512","DOIUrl":"10.1177/17534259211001512","url":null,"abstract":"<p><p>NK cells are the major lymphocyte subset of the innate immune system that mediates antiviral and anti-tumor responses. It is well established that they develop mechanisms to distinguish self from non-self during the process of NK cell education. Unlike T and B cells, natural killer cells lack clonotypic receptors and are activated after recognizing their target via germline-encoded receptors through natural cytotoxicity, cytokine stimulation, and Ab-dependent cellular cytotoxicity. Subsequently, they utilize cytotoxic granules, death receptor ligands, and cytokines to perform their effector functions. In this review, we provide a general overview of human NK cells, as opposed to murine NK cells, discussing their ontogeny, maturation, receptor diversity, types of responses, and effector functions. Furthermore, we also describe recent advances in human NK cell biology, including tissue-resident NK cell populations, NK cell memory, and novel approaches used to target NK cells in cancer immunotherapy.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"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/31/a9/10.1177_17534259211001512.PMC8054151.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25512602","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
Existence of natural mouse IgG mAbs recognising epitopes shared by malondialdehyde acetaldehyde adducts and Porphyromonas gingivalis. 存在识别丙二醛乙醛加合物和牙龈卟啉单胞菌共有表位的天然小鼠IgG单抗。
IF 3.2 4区 医学
Innate Immunity Pub Date : 2021-02-01 Epub Date: 2021-01-14 DOI: 10.1177/1753425920981133
Mikael Kyrklund, Heidi Kaski, Ramin Akhi, Antti E Nissinen, Outi Kummu, Ulrich Bergmann, Pirkko Pussinen, Sohvi Hörkkö, Chunguang Wang
{"title":"Existence of natural mouse IgG mAbs recognising epitopes shared by malondialdehyde acetaldehyde adducts and <i>Porphyromonas gingivalis</i>.","authors":"Mikael Kyrklund,&nbsp;Heidi Kaski,&nbsp;Ramin Akhi,&nbsp;Antti E Nissinen,&nbsp;Outi Kummu,&nbsp;Ulrich Bergmann,&nbsp;Pirkko Pussinen,&nbsp;Sohvi Hörkkö,&nbsp;Chunguang Wang","doi":"10.1177/1753425920981133","DOIUrl":"https://doi.org/10.1177/1753425920981133","url":null,"abstract":"<p><p>Natural Abs are produced by B lymphocytes in the absence of external Ag stimulation. They recognise self, altered self and foreign Ags, comprising an important first-line defence against invading pathogens and serving as innate recognition receptors for tissue homeostasis. Natural IgG Abs have been found in newborns and uninfected individuals. Yet, their physiological role remains unclear. Previously, no natural IgG Abs to oxidation-specific epitopes have been reported. Here, we show the cloning and characterisation of mouse IgG mAbs against malondialdehyde acetaldehyde (MAA)-modified low-density lipoprotein. Sequence analysis reveals high homology with germline genes, suggesting that they are natural. Further investigation shows that the MAA-specific natural IgG Abs cross-react with the major periodontal pathogen <i>Porphyromonas gingivalis</i> and recognise its principle virulence factors gingipain Kgp and long fimbriae. The study provides evidence that natural IgGs may play an important role in innate immune defence and in regulation of tissue homeostasis by recognising and removing invading pathogens and/or modified self-Ags, thus being involved in the development of periodontitis and atherosclerosis.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425920981133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38819924","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
Early prolonged neutrophil activation in critically ill patients with sepsis. 危重症脓毒症患者早期延长中性粒细胞活化。
IF 3.2 4区 医学
Innate Immunity Pub Date : 2021-02-01 Epub Date: 2021-01-18 DOI: 10.1177/1753425920980078
Sanna Törnblom, Sara Nisula, Suvi T Vaara, Meri Poukkanen, Sture Andersson, Ville Pettilä, Eero Pesonen
{"title":"Early prolonged neutrophil activation in critically ill patients with sepsis.","authors":"Sanna Törnblom,&nbsp;Sara Nisula,&nbsp;Suvi T Vaara,&nbsp;Meri Poukkanen,&nbsp;Sture Andersson,&nbsp;Ville Pettilä,&nbsp;Eero Pesonen","doi":"10.1177/1753425920980078","DOIUrl":"https://doi.org/10.1177/1753425920980078","url":null,"abstract":"<p><p>We hypothesised that plasma concentrations of biomarkers of neutrophil activation and pro-inflammatory cytokines differ according to the phase of rapidly evolving sepsis. In an observational study, we measured heparin-binding protein (HBP), myeloperoxidase (MPO), IL-6 and IL-8 in 167 sepsis patients on intensive care unit admission. We prospectively used the emergence of the first sepsis-associated organ dysfunction (OD) as a surrogate for the sepsis phase. Fifty-five patients (of 167, 33%) developed the first OD > 1 h before, 74 (44%) within ± 1 h, and 38 (23%) > 1 h after intensive care unit admission. HBP and MPO were elevated at a median of 12 h before the first OD, remained high up to 24 h, and were not associated with sepsis phase. IL-6 and IL-8 rose and declined rapidly close to OD emergence. Elevation of neutrophil activation markers HBP and MPO was an early event in the evolution of sepsis, lasting beyond the subsidence of the pro-inflammatory cytokine reaction. Thus, as sepsis biomarkers, HBP and MPO were not as prone as IL-6 and IL-8 to the effect of sample timing.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425920980078","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38833258","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
Comprehensive analysis of neuronal guidance cue expression regulation during monocyte-to-macrophage differentiation reveals post-transcriptional regulation of semaphorin7A by the RNA-binding protein quaking. 对单核细胞向巨噬细胞分化过程中神经元引导线索表达调控的全面分析揭示了 RNA 结合蛋白 quaking 对 semaphorin7A 的转录后调控。
IF 2.8 4区 医学
Innate Immunity Pub Date : 2021-02-01 Epub Date: 2020-11-26 DOI: 10.1177/1753425920966645
Huayu Zhang, Jurriën Prins, Dianne Vreeken, Barend W Florijn, Ruben G de Bruin, Oscar Rj van Hengel, Mieke F van Essen, Jacques Mgj Duijs, Hilde Van Esch, Eric P van der Veer, Anton Jan van Zonneveld, Janine M van Gils
{"title":"Comprehensive analysis of neuronal guidance cue expression regulation during monocyte-to-macrophage differentiation reveals post-transcriptional regulation of semaphorin7A by the RNA-binding protein quaking.","authors":"Huayu Zhang, Jurriën Prins, Dianne Vreeken, Barend W Florijn, Ruben G de Bruin, Oscar Rj van Hengel, Mieke F van Essen, Jacques Mgj Duijs, Hilde Van Esch, Eric P van der Veer, Anton Jan van Zonneveld, Janine M van Gils","doi":"10.1177/1753425920966645","DOIUrl":"10.1177/1753425920966645","url":null,"abstract":"<p><p>In response to inflammatory cytokines and chemokines, monocytes differentiate into macrophages. Comprehensive analysis of gene expression regulation of neuronal guidance cue (NGC) ligands and receptors in the monocyte-to-macrophage differentiation process is not available yet. We performed transcriptome profiling in both human primary PBMCs/PBMC-derived macrophages and THP-1 cells/THP-1-macrophages using microarray or RNA sequencing methods. Pathway analysis showed that the axonal guidance pathway is significantly regulated upon monocyte differentiation. We confirmed NGC ligands and receptors which were consistently regulated, including SEMA4D, SEMA7A, NRP1, NRP2, PLXNA1 and PLXNA3. The involvement of RNA-binding protein quaking (QKI) in the regulation of NGC expression was investigated using monocytes and macrophages from a QKI haplo-insufficient patient and her healthy sibling. This revealed a positive correlation of SEMA7A expression with QKI expression. <i>In silico</i> analysis of 3'UTRs of NGCs proposed the competitive binding of QKI to proximal microRNA targeting sites as the mechanism of QKI-dependent regulation of SEMA7A. RNA immunoprecipitation confirmed an interaction of QKI with the 3'UTR of SEMA7A. Loss of SEMA7A resulted in monocyte differentiation towards a more anti-inflammatory macrophage. Taken together, the axonal guidance pathway is regulated during monocyte-to-macrophage differentiation, and the regulation is in line with the necessary functional adaption for the specialised role of macrophages.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38655465","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
cAMP levels regulate macrophage alternative activation marker expression. cAMP水平调节巨噬细胞替代激活标志物的表达。
IF 3.2 4区 医学
Innate Immunity Pub Date : 2021-02-01 Epub Date: 2020-11-26 DOI: 10.1177/1753425920975082
Swamy Polumuri, Darren J Perkins, Stefanie N Vogel
{"title":"cAMP levels regulate macrophage alternative activation marker expression.","authors":"Swamy Polumuri,&nbsp;Darren J Perkins,&nbsp;Stefanie N Vogel","doi":"10.1177/1753425920975082","DOIUrl":"https://doi.org/10.1177/1753425920975082","url":null,"abstract":"<p><p>The capacity for macrophages to polarize into distinct functional activation states (e.g., M1, M2) is critical to tune an inflammatory response to the relevant infection or injury. Alternative or M2 polarization of macrophages is most often achieved <i>in vitro</i> in response to IL-4/IL-13 and results in the transcriptional up-regulation of a constellation of characteristic M2 marker genes. <i>In vivo</i>, additional signals from the inflammatory milieu can further increase or decrease M2 marker expression. Particularly, activation of cAMP-generating G protein-coupled receptors is reported to increase M2 markers, but whether this is strictly dependent upon cAMP production is unclear. We report herein that increased cAMP alone can increase IL-4-dependent M2 marker expression through a PKA/C/EBPβ/CREB dependent pathway in murine macrophages.</p>","PeriodicalId":13676,"journal":{"name":"Innate Immunity","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1753425920975082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38655466","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: 17
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