当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.

TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.

Abstract：

:Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evokes Ca(2+) influx through TRPM2 to activate Ca(2+)-dependent tyrosine kinase Pyk2 and amplify Erk signaling via Ras GTPase. This elicits nuclear translocation of nuclear factor-kappaB essential for the production of the chemokine interleukin-8 (CXCL8). In monocytes from Trpm2-deficient mice, H(2)O(2)-induced Ca(2+) influx and production of the macrophage inflammatory protein-2 (CXCL2), the mouse CXCL8 functional homolog, were impaired. In the dextran sulfate sodium-induced colitis inflammation model, CXCL2 expression, neutrophil infiltration and ulceration were attenuated by Trpm2 disruption. Thus, TRPM2 Ca(2+) influx controls the ROS-induced signaling cascade responsible for chemokine production, which aggravates inflammation. We propose functional inhibition of TRPM2 channels as a new therapeutic strategy for treating inflammatory diseases.

journal_name

Nat Med

journal_title

Nature medicine

authors

Yamamoto S,Shimizu S,Kiyonaka S,Takahashi N,Wajima T,Hara Y,Negoro T,Hiroi T,Kiuchi Y,Okada T,Kaneko S,Lange I,Fleig A,Penner R,Nishi M,Takeshima H,Mori Y

doi

10.1038/nm1758

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

738-47

issue

7

eissn

1078-8956

issn

1546-170X

pii

nm1758

journal_volume

14

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study.

    abstract：:Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation...

    journal_title：Nature medicine

    pub_type： 杂志文章,多中心研究

    doi：10.1038/nm.1790

    authors： Director's Challenge Consortium for the Molecular Classification of Lung Adenocarcinoma.,Shedden K,Taylor JM,Enkemann SA,Tsao MS,Yeatman TJ,Gerald WL,Eschrich S,Jurisica I,Giordano TJ,Misek DE,Chang AC,Zhu CQ,Strumpf D,Hanash

    更新日期：2008-08-01 00:00:00

  • Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. The Multicenter AIDS Cohort Study.

    abstract：:We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident hu...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0795-674

    authors： Margolick JB,Muñoz A,Donnenberg AD,Park LP,Galai N,Giorgi JV,O'Gorman MR,Ferbas J

    更新日期：1995-07-01 00:00:00

  • Genomic signatures to guide the use of chemotherapeutics.

    abstract：:Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signature...

    journal_title：Nature medicine

    pub_type： 杂志文章,收录出版

    doi：10.1038/nm1491

    authors： Potti A,Dressman HK,Bild A,Riedel RF,Chan G,Sayer R,Cragun J,Cottrill H,Kelley MJ,Petersen R,Harpole D,Marks J,Berchuck A,Ginsburg GS,Febbo P,Lancaster J,Nevins JR

    更新日期：2006-11-01 00:00:00

  • Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model for HIV-associated neurotoxicity.

    abstract：:HIV infection can cause extensive neuronal loss and clinically a severe dementia. The cause of the neurotoxicity remains unclear as neurons are not infected, but disturbance of glutamate-linked calcium entry has been implicated. In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA an...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1195-1174

    authors： Everall IP,Hudson L,al-Sarraj S,Honavar M,Lantos P,Kerwin R

    更新日期：1995-11-01 00:00:00

  • Notch3 signaling promotes the development of pulmonary arterial hypertension.

    abstract：:Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevati...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2021

    authors： Li X,Zhang X,Leathers R,Makino A,Huang C,Parsa P,Macias J,Yuan JX,Jamieson SW,Thistlethwaite PA

    更新日期：2009-11-01 00:00:00

  • Getting biological about the genetics of diabetes.

    abstract：:New technology has provided methods for collecting large amounts of data reflecting gene expression, metabolite and protein abundance, and post-translational modification of proteins. Integration of these various data sets enable the genetic mapping of many new phenotypes and facilitates the creation of network models...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0410-388

    authors： Newgard CB,Attie AD

    更新日期：2010-04-01 00:00:00

  • The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.

    abstract：:Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1574

    authors： Nakai A,Yamaguchi O,Takeda T,Higuchi Y,Hikoso S,Taniike M,Omiya S,Mizote I,Matsumura Y,Asahi M,Nishida K,Hori M,Mizushima N,Otsu K

    更新日期：2007-05-01 00:00:00

  • External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.

    abstract：:Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferat...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0298-235

    authors： Mehta D,George SJ,Jeremy JY,Izzat MB,Southgate KM,Bryan AJ,Newby AC,Angelini GD

    更新日期：1998-02-01 00:00:00

  • HIV-specific mucosal and cellular immunity in HIV-seronegative partners of HIV-seropositive individuals.

    abstract：:HIV-specific mucosal and cellular immunity was analyzed in heterosexual couples discordant for HIV status in serum and in HIV-unexposed controls. HIV-specific IgA but not IgG was present in urine and vaginal wash samples from HIV-exposed seronegative individuals (ESN), whereas both IgA and IgG were observed in their H...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1197-1250

    authors： Mazzoli S,Trabattoni D,Lo Caputo S,Piconi S,Blé C,Meacci F,Ruzzante S,Salvi A,Semplici F,Longhi R,Fusi ML,Tofani N,Biasin M,Villa ML,Mazzotta F,Clerici M

    更新日期：1997-11-01 00:00:00

  • The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals.

    abstract：:Recent studies suggest that statins can function to protect the vasculature in a manner that is independent of their lipid-lowering activity. We show here that statins rapidly activate the protein kinase Akt/PKB in endothelial cells. Accordingly, simvastatin enhanced phosphorylation of the endogenous Akt substrate end...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/79510

    authors： Kureishi Y,Luo Z,Shiojima I,Bialik A,Fulton D,Lefer DJ,Sessa WC,Walsh K

    更新日期：2000-09-01 00:00:00

  • SOCS-3 regulates onset and maintenance of T(H)2-mediated allergic responses.

    abstract：:Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation bet...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm896

    authors： Seki Y,Inoue H,Nagata N,Hayashi K,Fukuyama S,Matsumoto K,Komine O,Hamano S,Himeno K,Inagaki-Ohara K,Cacalano N,O'Garra A,Oshida T,Saito H,Johnston JA,Yoshimura A,Kubo M

    更新日期：2003-08-01 00:00:00

  • Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys.

    abstract：:Natural killer (NK) cells play an essential role in antiviral immunity, but knowledge of their function in secondary lymphoid organs is incomplete. Lymph node follicles constitute a major viral reservoir during infections with HIV-1 and simian immunodeficiency virus of macaques (SIVmac). In contrast, during nonpathoge...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4421

    authors： Huot N,Jacquelin B,Garcia-Tellez T,Rascle P,Ploquin MJ,Madec Y,Reeves RK,Derreudre-Bosquet N,Müller-Trutwin M

    更新日期：2017-11-01 00:00:00

  • Inhibition of cellular ras prevents smooth muscle cell proliferation after vascular injury in vivo.

    abstract：:Proliferation of smooth muscle cells of the arterial wall in response to local injury is an important aetiologic factor of vascular proliferative disorders such as atherosclerosis and restenosis after angioplasty. Ras proteins are key transducers of mitogenic signals from membrane to nucleus in many cell types. We inv...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0695-541

    authors： Indolfi C,Avvedimento EV,Rapacciuolo A,Di Lorenzo E,Esposito G,Stabile E,Feliciello A,Mele E,Giuliano P,Condorelli G

    更新日期：1995-06-01 00:00:00

  • A point mutation in KINDLIN3 ablates activation of three integrin subfamilies in humans.

    abstract：:Monogenic deficiency diseases provide unique opportunities to define the contributions of individual molecules to human physiology and to identify pathologies arising from their dysfunction. Here we describe a deficiency disease in two human siblings that presented with severe bleeding, frequent infections and osteope...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1917

    authors： Malinin NL,Zhang L,Choi J,Ciocea A,Razorenova O,Ma YQ,Podrez EA,Tosi M,Lennon DP,Caplan AI,Shurin SB,Plow EF,Byzova TV

    更新日期：2009-03-01 00:00:00

  • Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo.

    abstract：:Modest clinical outcomes of dendritic-cell (DC) vaccine trials call for the refinement of DC vaccine design. Although many potential antigens have been identified, development of methods to enhance antigen presentation by DCs has lagged. We have engineered a potent, drug-inducible CD40 (iCD40) receptor that permits te...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1183

    authors： Hanks BA,Jiang J,Singh RA,Song W,Barry M,Huls MH,Slawin KM,Spencer DM

    更新日期：2005-02-01 00:00:00

  • Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.

    abstract：:Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/84643

    authors： Skobe M,Hawighorst T,Jackson DG,Prevo R,Janes L,Velasco P,Riccardi L,Alitalo K,Claffey K,Detmar M

    更新日期：2001-02-01 00:00:00

  • Clinical microfluidics for neutrophil genomics and proteomics.

    abstract：:Neutrophils have key roles in modulating the immune response. We present a robust methodology for rapidly isolating neutrophils directly from whole blood with 'on-chip' processing for mRNA and protein isolation for genomics and proteomics. We validate this device with an ex vivo stimulation experiment and by compariso...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2205

    authors： Kotz KT,Xiao W,Miller-Graziano C,Qian WJ,Russom A,Warner EA,Moldawer LL,De A,Bankey PE,Petritis BO,Camp DG 2nd,Rosenbach AE,Goverman J,Fagan SP,Brownstein BH,Irimia D,Xu W,Wilhelmy J,Mindrinos MN,Smith RD,Davis RW

    更新日期：2010-09-01 00:00:00

  • GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes.

    abstract：:GLUT4, the insulin-responsive glucose transporter, plays an important role in postprandial glucose disposal. Altered GLUT4 activity is suggested to be one of the factors responsible for decreased glucose uptake in muscle and adipose tissue in obesity and diabetes. To assess the effect of GLUT4 expression on whole-body...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1097-1096

    authors： Stenbit AE,Tsao TS,Li J,Burcelin R,Geenen DL,Factor SM,Houseknecht K,Katz EB,Charron MJ

    更新日期：1997-10-01 00:00:00

  • TLR4 enhances TGF-beta signaling and hepatic fibrosis.

    abstract：:Hepatic injury is associated with a defective intestinal barrier and increased hepatic exposure to bacterial products. Here we report that the intestinal bacterial microflora and a functional Toll-like receptor 4 (TLR4), but not TLR2, are required for hepatic fibrogenesis. Using Tlr4-chimeric mice and in vivo lipopoly...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1663

    authors： Seki E,De Minicis S,Osterreicher CH,Kluwe J,Osawa Y,Brenner DA,Schwabe RF

    更新日期：2007-11-01 00:00:00

  • Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease.

    abstract：:Huntington's disease (HD) is a fatal dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion leading to an elongated polyglutamine stretch in huntingtin. Mutant huntingtin (mHTT) is ubiquitously expressed in all cells but elicits selective cortical and striatal neurodegeneration in HD. The mec...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3514

    authors： Wang N,Gray M,Lu XH,Cantle JP,Holley SM,Greiner E,Gu X,Shirasaki D,Cepeda C,Li Y,Dong H,Levine MS,Yang XW

    更新日期：2014-05-01 00:00:00

  • Natural adjuvants: endogenous activators of dendritic cells.

    abstract：:Dendritic cells, the most potent antigen-presenting cells, need to be activated before they can function to initiate an immune response. We report here that, in the absence of any foreign substances, dendritic cells can be activated by endogenous signals received from cells that are stressed, virally infected or kille...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/15200

    authors： Gallucci S,Lolkema M,Matzinger P

    更新日期：1999-11-01 00:00:00

  • SUMOylation of Krüppel-like transcription factor 5 acts as a molecular switch in transcriptional programs of lipid metabolism involving PPAR-delta.

    abstract：:Obesity and metabolic syndrome are increasingly recognized as major risk factors for cardiovascular disease. Herein we show that Krüppel-like transcription factor 5 (KLF5) is a crucial regulator of energy metabolism. Klf5(+/-) mice were resistant to high fat-induced obesity, hypercholesterolemia and glucose intoleranc...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1756

    authors： Oishi Y,Manabe I,Tobe K,Ohsugi M,Kubota T,Fujiu K,Maemura K,Kubota N,Kadowaki T,Nagai R

    更新日期：2008-06-01 00:00:00

  • Autocrine activation of the MET receptor tyrosine kinase in acute myeloid leukemia.

    abstract：:Although the treatment of acute myeloid leukemia (AML) has improved substantially in the past three decades, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating the aberrant growth and surviva...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2819

    authors： Kentsis A,Reed C,Rice KL,Sanda T,Rodig SJ,Tholouli E,Christie A,Valk PJ,Delwel R,Ngo V,Kutok JL,Dahlberg SE,Moreau LA,Byers RJ,Christensen JG,Vande Woude G,Licht JD,Kung AL,Staudt LM,Look AT

    更新日期：2012-07-01 00:00:00

  • Mechanisms of NAFLD development and therapeutic strategies.

    abstract：:There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosi...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/s41591-018-0104-9

    authors： Friedman SL,Neuschwander-Tetri BA,Rinella M,Sanyal AJ

    更新日期：2018-07-01 00:00:00

  • Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.

    abstract：:Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumo...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4055

    authors： Camarda R,Zhou AY,Kohnz RA,Balakrishnan S,Mahieu C,Anderton B,Eyob H,Kajimura S,Tward A,Krings G,Nomura DK,Goga A

    更新日期：2016-04-01 00:00:00

  • The natural killer T-cell ligand alpha-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice.

    abstract：:Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. V alpha 14-J alpha 15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0901-1052

    authors： Hong S,Wilson MT,Serizawa I,Wu L,Singh N,Naidenko OV,Miura T,Haba T,Scherer DC,Wei J,Kronenberg M,Koezuka Y,Van Kaer L

    更新日期：2001-09-01 00:00:00

  • Glutaminyl cyclase inhibition attenuates pyroglutamate Abeta and Alzheimer's disease-like pathology.

    abstract：:Because of their abundance, resistance to proteolysis, rapid aggregation and neurotoxicity, N-terminally truncated and, in particular, pyroglutamate (pE)-modified Abeta peptides have been suggested as being important in the initiation of pathological cascades resulting in the development of Alzheimer's disease. We fou...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1872

    authors： Schilling S,Zeitschel U,Hoffmann T,Heiser U,Francke M,Kehlen A,Holzer M,Hutter-Paier B,Prokesch M,Windisch M,Jagla W,Schlenzig D,Lindner C,Rudolph T,Reuter G,Cynis H,Montag D,Demuth HU,Rossner S

    更新日期：2008-10-01 00:00:00

  • Wearable sensor data and self-reported symptoms for COVID-19 detection.

    abstract：:Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-1123-x

    authors： Quer G,Radin JM,Gadaleta M,Baca-Motes K,Ariniello L,Ramos E,Kheterpal V,Topol EJ,Steinhubl SR

    更新日期：2021-01-01 00:00:00

  • Large-scale proteomic analysis of Alzheimer's disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation.

    abstract：:Our understanding of Alzheimer's disease (AD) pathophysiology remains incomplete. Here we used quantitative mass spectrometry and coexpression network analysis to conduct the largest proteomic study thus far on AD. A protein network module linked to sugar metabolism emerged as one of the modules most significantly ass...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-0815-6

    authors： Johnson ECB,Dammer EB,Duong DM,Ping L,Zhou M,Yin L,Higginbotham LA,Guajardo A,White B,Troncoso JC,Thambisetty M,Montine TJ,Lee EB,Trojanowski JQ,Beach TG,Reiman EM,Haroutunian V,Wang M,Schadt E,Zhang B,Dickson DW

    更新日期：2020-05-01 00:00:00

  • Anti-cancer activity of targeted pro-apoptotic peptides.

    abstract：:We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. T...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/12469

    authors： Ellerby HM,Arap W,Ellerby LM,Kain R,Andrusiak R,Rio GD,Krajewski S,Lombardo CR,Rao R,Ruoslahti E,Bredesen DE,Pasqualini R

    更新日期：1999-09-01 00:00:00