ATP-Induced Inflammasome Activation and Pyroptosis Is Regulated by AMP-Activated Protein Kinase in Macrophages.

Abstract:

:Adenosine triphosphate (ATP) is released by bacteria and host cells during bacterial infection as well as sterile tissue injury, acting as an inducer of inflammasome activation. Previous studies have shown that ATP treatment leads to AMP-activated protein kinase (AMPK) activation. However, it is unclear whether AMPK signaling has been involved in the regulation of ATP-induced inflammasome activation and subsequent pyroptosis. In this study, we aimed to investigate this issue in lipopolysaccharide-activated murine macrophages. Our results showed that AMPK signaling was activated in murine macrophages upon ATP treatment, which was accompanied by inflammasome activation and pyroptosis as evidenced by rapid cell membrane rupture as well as mature interleukin (IL)-1β and active caspase-1p10 release. The ATP-induced inflammasome activation and pyroptosis were markedly suppressed by an AMPK inhibitor compound C or small-interfering RNA-mediated knockdown of AMPKα, but could be greatly enhanced by metformin (a well-known AMPK agonist). Importantly, metformin administration increased the mortality of mice with bacterial sepsis, which was likely because metformin treatment enhanced the systemic inflammasome activation as indicated by elevated serum and hepatic IL-1β levels. Collectively, these data indicated that the AMPK signaling positively regulated ATP-induced inflammasome activation and pyroptosis in macrophages, highlighting the possibility of AMPK-targeting therapies for inflammatory diseases involving inflammasome activation.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Zha QB,Wei HX,Li CG,Liang YD,Xu LH,Bai WJ,Pan H,He XH,Ouyang DY

doi

10.3389/fimmu.2016.00597

subject

Has Abstract

pub_date

2016-12-12 00:00:00

pages

597

issn

1664-3224

journal_volume

7

pub_type

杂志文章
  • B7/CD28 in central tolerance: costimulation promotes maturation of regulatory T cell precursors and prevents their clonal deletion.

    abstract::According to the "two-step model," the intrathymic generation of CD4⁺ regulatory T (T(reg)) cells segregates into a first, T cell receptor (TCR)-driven phase and a second, cytokine-dependent phase. The initial TCR stimulus gives rise to a CD25⁺Foxp3⁻ developmental intermediate. These precursors subsequently require cy...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2011.00030

    authors: Hinterberger M,Wirnsberger G,Klein L

    更新日期:2011-07-25 00:00:00

  • Transcription Factor KLF10 Constrains IL-17-Committed Vγ4+ γδ T Cells.

    abstract::γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00196

    authors: Kim G,Gu MJ,Kim SJ,Ko KH,Kye YC,Kim CG,Cho JH,Lee WK,Song KD,Chu H,Park YM,Han SH,Yun CH

    更新日期:2018-02-28 00:00:00

  • Intravital Microscopic Evaluation of the Effects of a CXCR2 Antagonist in a Model of Liver Ischemia Reperfusion Injury in Mice.

    abstract:Background:Ischemia-reperfusion (IR) is a major contributor to graft rejection after liver transplantation. During IR injury, an intense inflammatory process occurs in the liver. Neutrophils are considered central players in the events that lead to liver injury. CXC chemokines mediate hepatic inflammation following rep...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01917

    authors: de Oliveira THC,Marques PE,Poosti F,Ruytinx P,Amaral FA,Brandolini L,Allegretti M,Proost P,Teixeira MM

    更新日期:2018-01-05 00:00:00

  • Cytoskeletal Protein 4.1R Is a Positive Regulator of the FcεRI Signaling and Chemotaxis in Mast Cells.

    abstract::Protein 4.1R, a member of the 4.1 family, functions as a bridge between cytoskeletal and plasma membrane proteins. It is expressed in T cells, where it binds to a linker for activation of T cell (LAT) family member 1 and inhibits its phosphorylation and downstream signaling events after T cell receptor triggering. The...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.03068

    authors: Draberova L,Draberova H,Potuckova L,Halova I,Bambouskova M,Mohandas N,Draber P

    更新日期:2020-01-14 00:00:00

  • A Threshold Model for T-Cell Activation in the Era of Checkpoint Blockade Immunotherapy.

    abstract::Continued discoveries of negative regulators of inflammatory signaling provide detailed molecular insights into peripheral tolerance and anti-tumor immunity. Accumulating evidence indicates that peripheral tolerance is maintained at multiple levels of immune responses by negative regulators of proinflammatory signalin...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00491

    authors: Guram K,Kim SS,Wu V,Sanders PD,Patel S,Schoenberger SP,Cohen EEW,Chen SY,Sharabi AB

    更新日期:2019-03-18 00:00:00

  • Pronounced Diurnal Pattern of Salivary C-Reactive Protein (CRP) With Modest Associations to Circulating CRP Levels.

    abstract::C-reactive protein (CRP), a humoral component of the innate immune system with important functions in host-defense, is extensively used as a sensitive biomarker of systemic inflammation. During inflammation, hepatocyte-derived CRP rises dramatically in the blood due to increased interleukin-6 (IL-6) levels. Reliable d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.607166

    authors: Wetterö J,von Löhneysen S,Cobar F,Kristenson M,Garvin P,Sjöwall C

    更新日期:2021-01-08 00:00:00

  • IL-21 Biased Alemtuzumab Induced Chronic Antibody-Mediated Rejection Is Reversed by LFA-1 Costimulation Blockade.

    abstract::Despite its excellent efficacy in controlling T cell mediated acute rejection, lymphocyte depletion may promote a humoral response. While T cell repopulation after depletion has been evaluated in many aspects, the B cell response has not been fully elucidated. We tested the hypothesis that the mechanisms also involve ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02323

    authors: Kwun J,Park J,Yi JS,Farris AB,Kirk AD,Knechtle SJ

    更新日期:2018-10-15 00:00:00

  • Oxidized Hemoglobin Is Antigenic and Immunogenic in Lupus.

    abstract::Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunolo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00732

    authors: Jain S,Bose A,Bastia B,Sharma H,Sachdeva R,Jain AK,Pal R

    更新日期:2017-06-26 00:00:00

  • c-Abl-TWIST1 Epigenetically Dysregulate Inflammatory Responses during Mycobacterial Infection by Co-Regulating Bone Morphogenesis Protein and miR27a.

    abstract::Mycobacteria propelled modulation of host responses is of considerable interest in the face of emerging drug resistance. Although it is known that Abl tyrosine kinases affect entry and persistence of mycobacteria, mechanisms that couple c-Abl to proximal signaling pathways during immunity are poorly understood. Loss-o...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00085

    authors: Mahadik K,Prakhar P,Rajmani RS,Singh A,Balaji KN

    更新日期:2018-02-01 00:00:00

  • What Is the Clinical Relevance of TNF Inhibitor Immunogenicity in the Management of Patients With Rheumatoid Arthritis?

    abstract::Tumor necrosis factor-α inhibitors (TNFis) have revolutionized the management of rheumatoid arthritis (RA), however despite considerable progress, only a small proportion of patients maintain long-term clinical response. Selection of, and switching between, biologics is mainly empirical, experiential, and not evidence...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00589

    authors: Mehta P,Manson JJ

    更新日期:2020-04-07 00:00:00

  • Is the A-Chain the Engine That Drives the Diversity of C1q Functions? Revisiting Its Unique Structure.

    abstract::The immunopathological functions associated with human C1q are still growing in terms of novelty, diversity, and pathologic relevance. It is, therefore, not surprising that C1q is being recognized as an important molecular bridge between innate and adaptive immunity. The secret of this functional diversity, in turn, r...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00162

    authors: Ghebrehiwet B,Kandov E,Kishore U,Peerschke EIB

    更新日期:2018-02-05 00:00:00

  • Limited Foxp3+ Regulatory T Cells Response During Acute Trypanosoma cruzi Infection Is Required to Allow the Emergence of Robust Parasite-Specific CD8+ T Cell Immunity.

    abstract::While it is now acknowledged that CD4+ T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by Trypanosoma cruzi was still poorly characterized. In order to understand...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02555

    authors: Araujo Furlan CL,Tosello Boari J,Rodriguez C,Canale FP,Fiocca Vernengo F,Boccardo S,Beccaria CG,Adoue V,Joffre O,Gruppi A,Montes CL,Acosta Rodriguez EV

    更新日期:2018-11-05 00:00:00

  • Immunological Aspect of Radiation-Induced Pneumonitis, Current Treatment Strategies, and Future Prospects.

    abstract::Delivery of high doses of radiation to thoracic region, particularly with non-small cell lung cancer patients, becomes difficult due to subsequent complications arising in the lungs of the patient. Radiation-induced pneumonitis is an early event evident in most radiation exposed patients observed within 2-4 months of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00506

    authors: Kainthola A,Haritwal T,Tiwari M,Gupta N,Parvez S,Tiwari M,Prakash H,Agrawala PK

    更新日期:2017-05-02 00:00:00

  • Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19).

    abstract::Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00827

    authors: Diao B,Wang C,Tan Y,Chen X,Liu Y,Ning L,Chen L,Li M,Liu Y,Wang G,Yuan Z,Feng Z,Zhang Y,Wu Y,Chen Y

    更新日期:2020-05-01 00:00:00

  • Arid5a Regulation and the Roles of Arid5a in the Inflammatory Response and Disease.

    abstract::Abnormal gene expression patterns underlie many diseases that represent major public health concerns and robust therapeutic challenges. Posttranscriptional gene regulation by RNA-binding proteins (RBPs) is well-recognized, and the biological functions of RBPs have been implicated in many diseases, such as autoimmune d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02790

    authors: Nyati KK,Agarwal RG,Sharma P,Kishimoto T

    更新日期:2019-12-05 00:00:00

  • Killed Whole-Cell Oral Cholera Vaccine Induces CCL20 Secretion by Human Intestinal Epithelial Cells in the Presence of the Short-Chain Fatty Acid, Butyrate.

    abstract::Short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral c...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00055

    authors: Sim JR,Kang SS,Lee D,Yun CH,Han SH

    更新日期:2018-01-29 00:00:00

  • Mesenchymal cell differentiation during lymph node organogenesis.

    abstract::Secondary lymphoid tissues such as lymph nodes are essential for the interactions between antigen presenting cells and lymphocytes that result in adaptive immune responses that protect the host against invading pathogens. The specialized architecture of these organs facilitates the cognate interactions between antigen...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00381

    authors: Brendolan A,Caamaño JH

    更新日期:2012-12-14 00:00:00

  • Emerging Mechanisms of Insulin-Mediated Antiviral Immunity in Drosophila melanogaster.

    abstract::Arboviruses (arthropod-borne viruses), such as Zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, include some of the most significant global health risks to human populations. The steady increase in the number of cases is of great concern due to the debilitating diseases associated with each viral infection. Beca...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02973

    authors: Trammell CE,Goodman AG

    更新日期:2019-12-20 00:00:00

  • Molecular and Cellular Dynamics in the Skin, the Lymph Nodes, and the Blood of the Immune Response to Intradermal Injection of Modified Vaccinia Ankara Vaccine.

    abstract::New vaccine design approaches would be greatly facilitated by a better understanding of the early systemic changes, and those that occur at the site of injection, responsible for the installation of a durable and oriented protective response. We performed a detailed characterization of very early infection and host re...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00870

    authors: Rosenbaum P,Tchitchek N,Joly C,Stimmer L,Hocini H,Dereuddre-Bosquet N,Beignon AS,Chapon C,Levy Y,Le Grand R,Martinon F

    更新日期:2018-04-25 00:00:00

  • Mycobacterium leprae-Specific Antibodies in Multibacillary Leprosy Patients Decrease During and After Treatment With Either the Regular 12 Doses Multidrug Therapy (MDT) or the Uniform 6 Doses MDT.

    abstract::Leprosy serology reflects the bacillary load of patients and multidrug therapy (MDT) reduces Mycobacterium leprae-specific antibody titers of multibacillary (MB) patients. The Clinical Trial for Uniform Multidrug Therapy Regimen for Leprosy Patients in Brazil (U-MDT/CT-BR) compared outcomes of regular 12 doses MDT/R-M...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.00915

    authors: Hungria EM,Bührer-Sékula S,Oliveira RM,Aderaldo LC,Pontes MAA,Cruz R,de Gonçalves HS,Penna MLF,Penna GO,Stefani MMA

    更新日期:2018-05-14 00:00:00

  • Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients.

    abstract::Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We perform...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00496

    authors: Lim SA,Kim J,Jeon S,Shin MH,Kwon J,Kim TJ,Im K,Han Y,Kwon W,Kim SW,Yee C,Kim SJ,Jang JY,Lee KM

    更新日期:2019-04-09 00:00:00

  • Modulation of Chemokine Responses: Synergy and Cooperativity.

    abstract::Chemokine biology is mediated by more complex interactions than simple monomolecular ligand-receptor interactions, as chemokines can form higher order quaternary structures, which can also be formed after binding to glycosaminoglycans (GAGs) on endothelial cells, and their receptors are found as dimers and/or oligomer...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2016.00183

    authors: Proudfoot AE,Uguccioni M

    更新日期:2016-05-19 00:00:00

  • Heme-Oxygenase-1 Expression Contributes to the Immunoregulation Induced by Fasciola hepatica and Promotes Infection.

    abstract::Fasciola hepatica, also known as the liver fluke, is a trematode that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. This parasite immunoregulates the host immune system by inducing a strong Th2 and regulatory T ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00883

    authors: Carasi P,Rodríguez E,da Costa V,Frigerio S,Brossard N,Noya V,Robello C,Anegón I,Freire T

    更新日期:2017-07-26 00:00:00

  • T Cell Metabolism: A New Perspective on Th17/Treg Cell Imbalance in Systemic Lupus Erythematosus.

    abstract::The Th17/T-regulatory (Treg) cell imbalance is involved in the occurrence and development of organ inflammation in systemic lupus erythematosus (SLE). Metabolic pathways can regulate T cell differentiation and function, thus contributing to SLE inflammation. Increasingly, data have shown metabolism influences and repr...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01027

    authors: Shan J,Jin H,Xu Y

    更新日期:2020-05-22 00:00:00

  • The Role of Natural Killer Cells in the Immune Response in Kidney Transplantation.

    abstract::Natural killer cells (NK) represent a population of lymphocytes involved in innate immune response. In addition to their role in anti-viral and anti-tumor defense, they also regulate several aspects of the allo-immune response in kidney transplant recipients. Growing evidence suggests a key role of NK cells in the pat...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01454

    authors: Pontrelli P,Rascio F,Castellano G,Grandaliano G,Gesualdo L,Stallone G

    更新日期:2020-07-23 00:00:00

  • Remote Activation of a Latent Epitope in an Autoantigen Decoded With Simulated B-Factors.

    abstract::Mutants of a catalytically inactive variant of Proteinase 3 (PR3)-iPR3-Val103 possessing a Ser195Ala mutation relative to wild-type PR3-Val103-offer insights into how autoantigen PR3 interacts with antineutrophil cytoplasmic antibodies (ANCAs) in granulomatosis with polyangiitis (GPA) and whether such interactions can...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02467

    authors: Pang YP,Casal Moura M,Thompson GE,Nelson DR,Hummel AM,Jenne DE,Emerling D,Volkmuth W,Robinson WH,Specks U

    更新日期:2019-10-25 00:00:00

  • G-CSF and G-CSFR Modulate CD4 and CD8 T Cell Responses to Promote Colon Tumor Growth and Are Potential Therapeutic Targets.

    abstract::Cytokines are known to shape the tumor microenvironment and although progress has been made in understanding their role in carcinogenesis, much remains to learn regarding their role in tumor growth and progression. We have identified granulocyte colony-stimulating factor (G-CSF) as one such cytokine, showing that G-CS...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01885

    authors: Karagiannidis I,Jerman SJ,Jacenik D,Phinney BB,Yao R,Prossnitz ER,Beswick EJ

    更新日期:2020-09-15 00:00:00

  • Correlation of Hsp70 Serum Levels with Gross Tumor Volume and Composition of Lymphocyte Subpopulations in Patients with Squamous Cell and Adeno Non-Small Cell Lung Cancer.

    abstract::Heat-shock protein 70 (Hsp70) is frequently found on the plasma membrane of a large number of malignant tumors including non-small cell lung cancer (NSCLC) and gets released into the blood circulation in lipid vesicles. On the one hand, a membrane (m)Hsp70-positive phenotype correlates with a high aggressiveness of th...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2015.00556

    authors: Gunther S,Ostheimer C,Stangl S,Specht HM,Mozes P,Jesinghaus M,Vordermark D,Combs SE,Peltz F,Jung MP,Multhoff G

    更新日期:2015-11-02 00:00:00

  • Piperlongumine Acts as an Immunosuppressant by Exerting Prooxidative Effects in Human T Cells Resulting in Diminished TH17 but Enhanced Treg Differentiation.

    abstract::Piperlongumine (PL), a natural small molecule derived from the Piper longum Linn plant, has received growing interest as a prooxidative drug with promising anticancer properties. Yet, the influence of PL on primary human T cells remained elusive. Knowledge of this is of crucial importance, however, since T cells in pa...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01172

    authors: Liang J,Ziegler JD,Jahraus B,Orlik C,Blatnik R,Blank N,Niesler B,Wabnitz G,Ruppert T,Hübner K,Balta E,Samstag Y

    更新日期:2020-06-12 00:00:00

  • Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differential Regulation and Correlation With Disease Activity.

    abstract::Galectins, a family of animal lectins, play central roles in immune system regulation, shaping both innate and adaptive responses in physiological and pathological processes. These include rheumatoid arthritis (RA), a chronic multifactorial autoimmune disease characterized by inflammatory responses that affects both a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.03057

    authors: Mendez-Huergo SP,Hockl PF,Stupirski JC,Maller SM,Morosi LG,Pinto NA,Berón AM,Musuruana JL,Nasswetter GG,Cavallasca JA,Rabinovich GA

    更新日期:2019-01-09 00:00:00