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Caspase-11 mediated inflammasome activation in macrophages by systemic infection of *** exacerbates arthritis

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International Journal of Oral Science 2024年第3期16卷 499-514页

作者： Tokuju Okano Hiroshi Ashida noriko Komatsu Masayuki Tsukasaki Tamako Iida Marie Iwasawa Yuto Takahashi Yasuo Takeuchi Takanori Iwata Miwa Sasai Masahiro Yamamoto Hiroshi Takayanagi Toshihiko Suzuki Department of Bacterial Pathogenesis Infection and Host ResponseGraduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of TokyoTokyoJapan Department of Lifetime Oral Health Care Science Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Periodontology Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan Department of Immunoparasitology Research Institute for Microbial DiseasesOsaka UniversityOsakaJapan

Clinical studies have shown that Aggregatibacter actinomycetemcomitans(***)is associated with aggressive periodontitis and can potentially trigger or exacerbate rheumatoid arthritis(RA).However,the mechanism is poorly ***,we show that systemic infection with *** triggers the progression of arthritis in mice anti-collagen antibody-induced arthritis(CAIA)model following IL-1βsecretion and cell infiltration in paws in a manner that is dependent on caspase-11-mediated inflammasome activation in *** administration of polymyxin B(PMB),chloroquine,and anti-CD11b antibody suppressed inflammasome activation in macrophages and arthritis in mice,suggesting that the recognition of lipopolysaccharide(LPS)in the cytosol after bacterial degradation by lysosomes and invasion via CD11b are needed to trigger arthritis following inflammasome activation in *** data reveal that the inhibition of caspase-11-mediated inflammasome activation potentiates aggravation of RA induced by infection with *** work highlights how RA can be progressed by inflammasome activation as a result of periodontitis-associated bacterial infection and discusses the mechanism of inflammasome activation in response to infection with ***.

关键词： CD11b inflam infection

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal Medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

The Implications of Population Decline and Fiscal Austerity on Public Nature:Insights From the Evolution of Urban Park Management System in Japan

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景观设计学（中英文） 2024年第4期12卷 8-25页

作者： Xizi XU Fumihiko SETA noriko AKITA Kai ZHOU School of Urban and Environmental Sciences Hunan University of TechnologyZhuzhou 412000China Department of Urban Engineering The University of TokyoTokyo 113-8654Japan Graduate School of Horticulture Chiba UniversityChiba 271-8510Japan Department of Urban and Rural Planning School of Architecture and PlanningHunan UniversityChangsha 410082China

Facing challenges of population decline and fiscal austerity,Japan has implemented a series of initiatives to promote public-private partnerships(PPP)to ensure the sustainability of urban parks and revitalize urban *** initiatives,while alleviating the government’s financial burdens on parks,have also raised concerns about the potential erosion of publicness and public interests resulted from the commercialization of public *** paper reviews the evolution of Japan’s urban park management system after World War II—including three phases of being purely public goods,initiating marketization,and diversifying management *** functions of parks have continuously enriched,and the construction,management,and operational modes have shifted from government-led towards multi-stakeholder participation,along with expanded funding *** examining the PPP types,driving forces,implementation mechanisms and challenges in urban park management,this paper points out that,in different eras and social contexts,the Japanese government has kept adjusting its role to maximize public *** has proactively updated the implications of publicness in infrastructure like urban parks,from a post-war opposite of publicness versus privateness on ownership,to the participation of private capital for a higher efficiency,and finally to a community for a stronger regional *** reforms of urban park management system in Japan offer significant lessons and insights for urban infrastructure management in other countries and regions.

关键词： Publicness Landscape Justice Public-Private Partnership “Private Finance Initiative”System for Parks Urban Parks Management System Urban Infrastructure

Identification of shared and unique gene families associated with oral clefts

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International Journal of Oral Science 2017年第2期9卷 104-109页

作者： noriko Funato Masataka Nakamura Department of Signal Gene Regulation Research Center for Medical and Dental SciencesTokyo Medical and Dental University1-5-45 YushimaBunkyo-kuTokyoJapan

Oral clefts, the most frequent congenital birth defects in humans, are multifactorial disorders caused by genetic and environmental factors. Epidemiological studies point to different etiologies underlying the oral cleft phenotypes, cleft lip(CL),CL and/or palate(CL/P) and cleft palate(CP). More than 350 genes have syndromic and/or nonsyndromic oral cleft associations in humans. Although genes related to genetic disorders associated with oral cleft phenotypes are known, a gap between detecting these associations and interpretation of their biological importance has remained. Here, using a gene ontology analysis approach, we grouped these candidate genes on the basis of different functional categories to gain insight into the genetic etiology of oral clefts. We identified different genetic profiles and found correlations between the functions of gene products and oral cleft phenotypes. Our results indicate inherent differences in the genetic etiologies that underlie oral cleft phenotypes and support epidemiological evidence that genes associated with CL/P are both developmentally and genetically different from CP only, incomplete CP, and submucous CP. The epidemiological differences among cleft phenotypes may reflect differences in the underlying genetic causes. Understanding the different causative etiologies of oral clefts is important as it may lead to improvements in diagnosis, counseling, and prevention.

关键词： cleft palate epidemiology gene ontology mutations soft palate syndrome

The impact of AI: can a robot get into the University of Tokyo?

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National Science Review 2015年第2期2卷 135-136页

作者： noriko H.Arai National Institute of Informatics

The ‘Todai Robot Project(Can a robot get into the University of Tokyo?)’ was initiated by the National Institute of Informatics(NII),the Japan’s only general academic research institution of informatics,in 2011 as ... 详细信息

关键词： can a robot get into the University of Tokyo The impact of AI

IgSF11-mediated phosphorylation of pyruvate kinase M2 regulates osteoclast differentiation and prevents pathological bone loss

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Bone Research 2023年第1期11卷 215-227页

作者： Hyunsoo Kim noriko Takegahara Yongwon Choi Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of MedicinePhiladelphiaPA19104USA

Osteoclasts are primary bone-resorbing cells,and receptor-activated NF-k B ligand(RANKL)stimulation is the key driver of osteoclast *** late-stage differentiation,osteoclasts become multinucleated and enlarged(so-called“maturation”),suggesting their need to adapt to changing metabolic demands and a substantial increase in ***,we demonstrate that immunoglobulin superfamily 11(Ig SF11),which is required for osteoclast differentiation through an association with the postsynaptic scaffolding protein PSD-95,regulates osteoclast differentiation by controlling the activity of pyruvate kinase M isoform2(PKM2).By using a system that directly induces the activation of Ig SF11 in a controlled manner,we identified PKM2 as a major Ig SF11-induced tyrosine-phosphorylated *** SF11 activates multiple Src family tyrosine kinases(SFKs),including c-Src,Fyn,and Hc K,which phosphorylate PKM2 and thereby inhibit PKM2 ***,Ig SF11-deficient cells show higher PKM2activity and defective osteoclast ***,inhibiting PKM2 activities with the specific inhibitor Shikonin rescues the impaired osteoclast differentiation in Ig SF11-deficient cells,and activating PKM2 with the specific activator TEPP46 suppresses osteoclast differentiation in wild-type ***,PKM2 activation further suppresses osteoclastic bone loss without affecting bone formation in *** together,these results show that Ig SF11 controls osteoclast differentiation through PKM2 activity,which is a metabolic switch necessary for optimal osteoclast maturation.

关键词： SF11 osteoclast impaired

Hydrogen production at intermediate temperatures with proton conducting ceramic cells:Electrocatalytic activity,durability and energy efficiency

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Journal of Energy Chemistry 2023年第11期86卷 437-446,I0010页

作者： Haoyu Zheng Feng Han noriko Sata Rémi Costa Institute of Engineering Thermodynamics German Aerospace Center (DLR) Institute for Building Energetics Thermotechnology and Energy Storage (IGTE) University of Stuttgart

Proton conducting ceramic cells(PCCs)are an attractive emerging technology operating in the intermediate temperature range of 500 to 700℃.In this work,we evaluate the production of hydrogen at intermediate temperatures by proton conducting ceramic cell electrolysis(PCCEL).We demonstrate a highperformance steam electrolysis owing to a composite positrode based on BaGd_(0.8)La_(0.2)Co_(2)O_(6-δ)(BGLC1082)and BaZr0.5Ce0.4Y0.1O3-δ(BZCY541).The high reliability of PCCEL is demonstrated for 1680 h at a current density as high as-0.8 A cm^(-2)close to the thermoneutral cell voltage at 600℃.The electrolysis cell showed a specific energy consumption ranging from 54 to 66 kW h kg^(-1)that is comparable to state-of-the-art low temperature electrolysis technologies,while showing hydrogen production rates systematically higher than commercial solid oxide ceramic cells(SOCs).Compared to SOCs,the results verified the higher performances of PCCs at the relevant operating temperatures,due to the lower activation energy for proton transfer comparing with oxygen ion ***,because of the p-type electronic conduction in protonic ceramics,the energy conversion rate of PCCs is relatively lower in steam *** faradaic efficiency of the PCC in electrolysis mode can be increased at lower operating temperatures and in endothermic conditions,making PCCEL a technology of choice to valorize high temperature waste heat from industrial processes into *** increase the faradaic efficiency by optimizing the materials,the cell design,or the operating strategy is a key challenge to address for future developments of PCCEL in order to achieve even more superior techno-economic merits.

关键词： Steam electrolysis Hydrogen production Proton conducting ceramics Intermediate temperature Energy efficiency

NF-κB Regulates B-Cell-Derived Nerve Growth Factor Expression

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Cellular & Molecular Immunology 2006年第1期3卷 63-66页

作者： Klaus Heese noriko Inoue Tohru Sawada Department of Molecular and Cell Biology School of Biological SciencesNanyang Technological University60 Nanyang DriveSingapore 637551Singapore BF Research Institute Inc.Itoyoshi Building 2012-5-9 DoshomachiChuo-kuOsaka 541-0045Japan BF Research Institute Inc. Itoyoshi Building 2012-5-9 DoshomachiChuo-kuOsaka 541-0045Japan

In the mammalian brain, four neurotrophins have been identified： nerve growth factor （NGF）, brain-derived neurotrophic factor （BDNF）, neurotrophin-3 （NT-3） and neurotrophin-4/5 （NT-4/5）. NGF exerts an important role in the development and functions of the central and peripheral nervous system. However, it has recently been documented that several types of immune cells, such as mast ceils, iymphocytes, basophils and eosinophils, produce, store and release NGF. Accumulating preclinical and clinical data indicate that dysfunctions of NGF and the other neurotrophins may contribute to impaired immune responses and concentration of NGF frequently correlates with disease severity. Thus, the aim of this study was to elucidate the potential signaling mechanisms of cytokineneurotrophins interactions contributing to increased NGF levels. Our data show that the transcription factor NF-κB plays a pivotal role in regulating B-cell-derived NGF expression.

关键词： immune system inflammation interleukin NGF neurotrophin

口腔幽门螺杆菌感染与胃幽门螺杆菌感染的相关性探讨

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中华消化杂志 2011年第7期31卷 470-473页

作者：叶国钦 Karin Everett noriko taylor 美国西雅图美利泰格诊断试剂有限公司螺旋杆菌研究所98208

目的分析口腔和胃幽门螺杆菌（Hp）感染的检测结果，探讨口腔Hp感染与胃Hp感染的相关性，及口腔Hp感染对Hp根除治疗的影响。方法采用唾液测定螺旋杆菌抗原技术（HPS）和^13C／^14C尿素呼气试验（UBT）同步检测的方法，对114例有上消化... 详细信息

目的分析口腔和胃幽门螺杆菌（Hp）感染的检测结果，探讨口腔Hp感染与胃Hp感染的相关性，及口腔Hp感染对Hp根除治疗的影响。方法采用唾液测定螺旋杆菌抗原技术（HPS）和^13C／^14C尿素呼气试验（UBT）同步检测的方法，对114例有上消化道症状的初诊患者（第1组），129例确诊为胃Hp感染经根除治疗后4周复查的患者（第2组）和33例无消化道症状的健康志愿者（第3组），进行口腔和胃Hp检测。结果第1组、第2组和第3组HPS阳性检出率分别为77．19％、75．97％和81．82％，3组比较差异无统计学意义（x^2=0．47，P值均〉0．05）；UBT阳性检出率第1组（52．63％）比第2组（34．11％）和第3组（21．21％）高，第1组与第2组和第3组比较，差异有统计学意义（x^2=8．48和10．19，P均〈0．05），第2组与第3组之间差异无统计学意义（x^2=2．03，P〉0．05）；在UBT阳性者中，HPS阳性检出率差异无统计学意义（3组分别为81．67％、88．64％和100％，x^2=2．25，P值均〉O．05）。结论唾液中存在高Hp抗原检出现象，口腔可能是Hp在胃以外的“第二定居地”。口服药物治疗对口腔Hp感染几乎无效，口腔Hp的存在可能是胃病发病和复发的一个重要和直接的原因。

关键词：螺杆菌幽门口腔胃抗原细菌唾液尿素碳放射性同位素