Prognostic Value of NLRP3 Inflammasome and TLR4
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TNF-Α Promotes Colon Cancer Cell Migration and Invasion by Upregulating TROP-2
3820 ONCOLOGY LETTERS 15: 3820-3827, 2018 TNF-α promotes colon cancer cell migration and invasion by upregulating TROP-2 PENG ZHAO and ZHONGTAO ZHANG Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China Received March 3, 2017; Accepted October 24, 2017 DOI: 10.3892/ol.2018.7735 Abstract. High levels of tumor-associated calcium signal but did not significantly affect p38 and JNK phosphoryla- transduction protein (TROP)-2 have been demonstrated to tion levels. Treatment with a specific ERK1/2 inhibitor be strongly associated with tumor necrosis factor (TNF)-α suppressed the TNF-α-induced upregulation of TROP-2 and levels in colon cancer. In the present study, the effect of the TNF-α-induced colon cancer cell migration and inva- TNF-α on the regulation of TROP-2 expression and its effect sion. In conclusion, the present results demonstrated that in colon cancer cell migration and invasion were investigated low concentrations of TNF-α significantly enhanced colon in vitro. TROP-2 protein levels were evaluated in HCT-116 cancer cell migration and invasion by upregulating TROP-2 human colon cancer cells cultured with various concentra- via the ERK1/2 signaling pathway. tions of TNF-α using western blot analysis. Changes in the migratory and invasive potential of the cells were evaluated Introduction using a wound healing and transwell assay, respectively. Then, TROP-2 expression was downregulated in cells by use Colon cancer is a common malignant tumor of the digestive of siRNA, and TROP‑2 knockdown was confirmed at the tract, from which morbidity and mortality have been increasing mRNA and protein level by reverse transcription-quantitative in recent years. -
Post-Translational Regulation of Inflammasomes
OPEN Cellular & Molecular Immunology (2017) 14, 65–79 & 2017 CSI and USTC All rights reserved 2042-0226/17 www.nature.com/cmi REVIEW Post-translational regulation of inflammasomes Jie Yang1,2, Zhonghua Liu1 and Tsan Sam Xiao1 Inflammasomes play essential roles in immune protection against microbial infections. However, excessive inflammation is implicated in various human diseases, including autoinflammatory syndromes, diabetes, multiple sclerosis, cardiovascular disorders and neurodegenerative diseases. Therefore, precise regulation of inflammasome activities is critical for adequate immune protection while limiting collateral tissue damage. In this review, we focus on the emerging roles of post-translational modifications (PTMs) that regulate activation of the NLRP3, NLRP1, NLRC4, AIM2 and IFI16 inflammasomes. We anticipate that these types of PTMs will be identified in other types of and less well-characterized inflammasomes. Because these highly diverse and versatile PTMs shape distinct inflammatory responses in response to infections and tissue damage, targeting the enzymes involved in these PTMs will undoubtedly offer opportunities for precise modulation of inflammasome activities under various pathophysiological conditions. Cellular & Molecular Immunology (2017) 14, 65–79; doi:10.1038/cmi.2016.29; published online 27 June 2016 Keywords: inflammasome; phosphorylation; post-translational modifications; ubiquitination INTRODUCTION upstream sensor molecules through its PYD domain and The innate immune system relies on pattern recognition downstream -
Genetic Variant in 3' Untranslated Region of the Mouse Pycard Gene
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.26.437184; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 1 2 3 Title: 4 Genetic Variant in 3’ Untranslated Region of the Mouse Pycard Gene Regulates Inflammasome 5 Activity 6 Running Title: 7 3’UTR SNP in Pycard regulates inflammasome activity 8 Authors: 9 Brian Ritchey1*, Qimin Hai1*, Juying Han1, John Barnard2, Jonathan D. Smith1,3 10 1Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 11 Cleveland, OH 44195 12 2Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 13 44195 14 3Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western 15 Reserve University, Cleveland, OH 44195 16 *, These authors contributed equally to this study. 17 Address correspondence to Jonathan D. Smith: email [email protected]; ORCID ID 0000-0002-0415-386X; 18 mailing address: Cleveland Clinic, Box NC-10, 9500 Euclid Avenue, Cleveland, OH 44195, USA. 19 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.03.26.437184; this version posted March 26, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. 20 Abstract 21 Quantitative trait locus mapping for interleukin-1 release after inflammasome priming and activation 22 was performed on bone marrow-derived macrophages (BMDM) from an AKRxDBA/2 strain intercross. -
ATP-Binding and Hydrolysis in Inflammasome Activation
molecules Review ATP-Binding and Hydrolysis in Inflammasome Activation Christina F. Sandall, Bjoern K. Ziehr and Justin A. MacDonald * Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; [email protected] (C.F.S.); [email protected] (B.K.Z.) * Correspondence: [email protected]; Tel.: +1-403-210-8433 Academic Editor: Massimo Bertinaria Received: 15 September 2020; Accepted: 3 October 2020; Published: 7 October 2020 Abstract: The prototypical model for NOD-like receptor (NLR) inflammasome assembly includes nucleotide-dependent activation of the NLR downstream of pathogen- or danger-associated molecular pattern (PAMP or DAMP) recognition, followed by nucleation of hetero-oligomeric platforms that lie upstream of inflammatory responses associated with innate immunity. As members of the STAND ATPases, the NLRs are generally thought to share a similar model of ATP-dependent activation and effect. However, recent observations have challenged this paradigm to reveal novel and complex biochemical processes to discern NLRs from other STAND proteins. In this review, we highlight past findings that identify the regulatory importance of conserved ATP-binding and hydrolysis motifs within the nucleotide-binding NACHT domain of NLRs and explore recent breakthroughs that generate connections between NLR protein structure and function. Indeed, newly deposited NLR structures for NLRC4 and NLRP3 have provided unique perspectives on the ATP-dependency of inflammasome activation. Novel molecular dynamic simulations of NLRP3 examined the active site of ADP- and ATP-bound models. The findings support distinctions in nucleotide-binding domain topology with occupancy of ATP or ADP that are in turn disseminated on to the global protein structure. -
PDGFR-Β+ Fibroblasts Deteriorate Survival in Human Solid Tumors: a Meta-Analysis
www.aging-us.com AGING 2021, Vol. 13, No. 10 Research Paper PDGFR-β+ fibroblasts deteriorate survival in human solid tumors: a meta-analysis Guoming Hu1,*, Liming Huang1,*, Kefang zhong1, Liwei Meng1, Feng Xu1, Shimin Wang2, Tao Zhang3,& 1Department of General Surgery (Breast and Thyroid Surgery), Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang 312000, China 2Department of Nephrology, Shaoxing People’s Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Zhejiang 312000, China 3Department of General Surgery III, Affiliated Hospital of Shaoxing University, Zhejiang 312000, China *Equal contribution Correspondence to: Tao Zhang, Guoming Hu; email: [email protected], https://orcid.org/0000-0001-7533-4900; [email protected] Keywords: tumor-infiltrating PDGFR-β+ fibroblasts, worse prognosis, solid tumor, meta-analysis Received: January 11, 2021 Accepted: April 2, 2021 Published: May 3, 2021 Copyright: © 2021 Hu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Fibroblasts are a highly heterogeneous population in tumor microenvironment. PDGFR-β+ fibroblasts, a subpopulation of activated fibroblasts, have proven to correlate with cancer progression through multiple of mechanisms including inducing angiogenesis and immune evasion. However, the prognostic role of these cells in solid tumors is still not conclusive. Herein, we carried out a meta-analysis including 24 published studies with 6752 patients searched from PubMed, Embase and EBSCO to better comprehend the value of such subpopulation in prognosis prediction for solid tumors. -
The Evolving Relationship of Wound Healing and Tumor Stroma
The evolving relationship of wound healing and tumor stroma Deshka S. Foster, … , Michael T. Longaker, Jeffrey A. Norton JCI Insight. 2018;3(18):e99911. https://doi.org/10.1172/jci.insight.99911. Review The stroma in solid tumors contains a variety of cellular phenotypes and signaling pathways associated with wound healing, leading to the concept that a tumor behaves as a wound that does not heal. Similarities between tumors and healing wounds include fibroblast recruitment and activation, extracellular matrix (ECM) component deposition, infiltration of immune cells, neovascularization, and cellular lineage plasticity. However, unlike a wound that heals, the edges of a tumor are constantly expanding. Cell migration occurs both inward and outward as the tumor proliferates and invades adjacent tissues, often disregarding organ boundaries. The focus of our review is cancer associated fibroblast (CAF) cellular heterogeneity and plasticity and the acellular matrix components that accompany these cells. We explore how similarities and differences between healing wounds and tumor stroma continue to evolve as research progresses, shedding light on possible therapeutic targets that can result in innovative stromal-based treatments for cancer. Find the latest version: https://jci.me/99911/pdf REVIEW The evolving relationship of wound healing and tumor stroma Deshka S. Foster,1,2 R. Ellen Jones,1 Ryan C. Ransom,1 Michael T. Longaker,1,2 and Jeffrey A. Norton1,2 1Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Division of Plastic and Reconstructive Surgery, and 2Department of Surgery, Stanford University School of Medicine, Stanford, California, USA. The stroma in solid tumors contains a variety of cellular phenotypes and signaling pathways associated with wound healing, leading to the concept that a tumor behaves as a wound that does not heal. -
A Role for the Nlr Family Members Nlrc4 and Nlrp3 in Astrocytic Inflammasome Activation and Astrogliosis
A ROLE FOR THE NLR FAMILY MEMBERS NLRC4 AND NLRP3 IN ASTROCYTIC INFLAMMASOME ACTIVATION AND ASTROGLIOSIS Leslie C. Freeman A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Curriculum of Genetics and Molecular Biology. Chapel Hill 2016 Approved by: Jenny P. Y. Ting Glenn K. Matsushima Beverly H. Koller Silva S. Markovic-Plese Pauline. Kay Lund ©2016 Leslie C. Freeman ALL RIGHTS RESERVED ii ABSTRACT Leslie C. Freeman: A Role for the NLR Family Members NLRC4 and NLRP3 in Astrocytic Inflammasome Activation and Astrogliosis (Under the direction of Jenny P.Y. Ting) The inflammasome is implicated in many inflammatory diseases but has been primarily studied in the macrophage-myeloid lineage. Here we demonstrate a physiologic role for nucleotide-binding domain, leucine-rich repeat, CARD domain containing 4 (NLRC4) in brain astrocytes. NLRC4 has been primarily studied in the context of gram-negative bacteria, where it is required for the maturation of pro-caspase-1 to active caspase-1. We show the heightened expression of NLRC4 protein in astrocytes in a cuprizone model of neuroinflammation and demyelination as well as human multiple sclerotic brains. Similar to macrophages, NLRC4 in astrocytes is required for inflammasome activation by its known agonist, flagellin. However, NLRC4 in astrocytes also mediate inflammasome activation in response to lysophosphatidylcholine (LPC), an inflammatory molecule associated with neurologic disorders. In addition to NLRC4, astrocytic NLRP3 is required for inflammasome activation by LPC. Two biochemical assays show the interaction of NLRC4 with NLRP3, suggesting the possibility of a NLRC4-NLRP3 co-inflammasome. -
Inflammasome Adaptor ASC Suppresses Apoptosis of Gastric Cancer Cells by an IL-18 Mediated Inflammation-Independent Mechanism
Author Manuscript Published OnlineFirst on December 27, 2017; DOI: 10.1158/0008-5472.CAN-17-1887 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Inflammasome adaptor ASC suppresses apoptosis of gastric cancer cells by an IL-18 mediated inflammation-independent mechanism Virginie Deswaerte1,2,*, Paul Nguyen3,4,*, Alison West1,2, Alison F. Browning1,2, Liang Yu1,2, Saleela M. Ruwanpura1,2, Jesse Balic1,2, Thaleia Livis1,2, Charlotte Girard5, Adele Preaudet3,4, Hiroko Oshima6, Ka Yee Fung3,4, Hazel Tye1,2, Meri Najdovska1,2, Matthias Ernst7, Masanobu Oshima6, Cem Gabay5, Tracy Putoczki3,4, and Brendan J. Jenkins1,2 1Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia; 2Department of Molecular Translational Science, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; 3Inflammation Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; 4Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; 5Division of Rheumatology, University Hospital of Geneva, and Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland; 6Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan; 7Olivia Newton-John Cancer Research Institute, La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia. *These authors contributed equally. Running title: ASC inflammasomes promote gastric cancer via IL-18 Keywords: apoptosis, ASC, gastric cancer, IL-18, inflammasomes. 1 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 2017 American Association for Cancer Research. Author Manuscript Published OnlineFirst on December 27, 2017; DOI: 10.1158/0008-5472.CAN-17-1887 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. -
Cutting Edge: Critical Role for PYCARD/ASC in the Development of Experimental Autoimmune Encephalomyelitis This Information Is Current As of September 26, 2021
Cutting Edge: Critical Role for PYCARD/ASC in the Development of Experimental Autoimmune Encephalomyelitis This information is current as of September 26, 2021. Patrick J. Shaw, John R. Lukens, Samir Burns, Hongbo Chi, Maureen A. McGargill and Thirumala-Devi Kanneganti J Immunol 2010; 184:4610-4614; Prepublished online 5 April 2010; doi: 10.4049/jimmunol.1000217 Downloaded from http://www.jimmunol.org/content/184/9/4610 Supplementary http://www.jimmunol.org/content/suppl/2010/04/06/jimmunol.100021 http://www.jimmunol.org/ Material 7.DC1 References This article cites 20 articles, 3 of which you can access for free at: http://www.jimmunol.org/content/184/9/4610.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 26, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Cutting Edge: Critical Role for PYCARD/ASC in the Development of Experimental Autoimmune Encephalomyelitis Patrick J. Shaw, John R. -
The NLRP3 and NLRP1 Inflammasomes Are Activated In
Saresella et al. Molecular Neurodegeneration (2016) 11:23 DOI 10.1186/s13024-016-0088-1 RESEARCHARTICLE Open Access The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer’s disease Marina Saresella1*†, Francesca La Rosa1†, Federica Piancone1, Martina Zoppis1, Ivana Marventano1, Elena Calabrese1, Veronica Rainone2, Raffaello Nemni1,3, Roberta Mancuso1 and Mario Clerici1,3 Abstract Background: Interleukin-1 beta (IL-1β) and its key regulator, the inflammasome, are suspected to play a role in the neuroinflammation observed in Alzheimer’s disease (AD); no conclusive data are nevertheless available in AD patients. Results: mRNA for inflammasome components (NLRP1, NLRP3, PYCARD, caspase 1, 5 and 8) and downstream effectors (IL-1β, IL-18) was up-regulated in severe and MILD AD. Monocytes co-expressing NLRP3 with caspase 1 or caspase 8 were significantly increased in severe AD alone, whereas those co-expressing NLRP1 and NLRP3 with PYCARD were augmented in both severe and MILD AD. Activation of the NLRP1 and NLRP3 inflammasomes in AD was confirmed by confocal microscopy proteins co-localization and by the significantly higher amounts of the pro-inflammatory cytokines IL-1β and IL-18 being produced by monocytes. In MCI, the expression of NLRP3, but not the one of PYCARD or caspase 1 was increased, indicating that functional inflammasomes are not assembled in these individuals: this was confirmed by lack of co-localization and of proinflammatory cytokines production. Conclusions: The activation of at least two different inflammasome complexes -
Monoclonal Antibodies in Cancer Therapy
Clin Oncol Cancer Res (2011) 8: 215–219 215 DOI 10.1007/s11805-011-0583-7 Monoclonal Antibodies in Cancer Therapy Yu-Ting GUO1,2 ABSTRACT Monoclonal antibodies (MAbs) are a relatively new Qin-Yu HOU1,2 innovation in cancer treatment. At present, some monoclonal antibodies have increased the efficacy of the treatment of certain 1,2 Nan WANG tumors with acceptable safety profiles. When monoclonal antibodies enter the body and attach to cancer cells, they function in several different ways: first, they can trigger the immune system to attack and kill that cancer cell; second, they can block the growth signals; third, they can prevent the formation of new blood vessels. Some naked 1 Key Laboratory of Industrial Fermentation MAbs such as rituximab can be directed to attach to the surface of Microbiology, Ministry of Education, Tianjin, cancer cells and make them easier for the immune system to find and 300457, China. destroy. The ability to produce antibodies with limited immunogeni- 2 Tianjin Key Laboratory of Industrial Micro- city has led to the production and testing of a host of agents, several biology, College of Biotechnology, Tianjin of which have demonstrated clinically important antitumor activity University of Science and Technology, Tianjin, 300457, China. and have received U.S. Food & Drug Administration (FDA) approval as cancer treatments. To reduce the immunogenicity of murine anti- bodies, murine molecules are engineered to remove the immuno- genic content and to increase their immunologic efficiency. Radiolabeled antibodies composed of antibodies conjugated to radionuclides show efficacy in non-Hodgkin’s lymphoma. Anti- vascular endothelial growth factor (VEGF) antibodies such as bevacizumab intercept the VEGF signal of tumors, thereby stopping them from connecting with their targets and blocking tumor growth. -
The Tumor Microenvironment Regulates Retinoblastoma Cell Survival
University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 12-2018 The umorT Microenvironment Regulates Retinoblastoma Cell Survival Zachary K. Goldsmith University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Eye Diseases Commons, Medical Cell Biology Commons, Neoplasms Commons, and the Ophthalmology Commons Recommended Citation Goldsmith, Zachary K. (http://orcid.org/0000-0002-7393-733), "The umorT Microenvironment Regulates Retinoblastoma Cell Survival" (2018). Theses and Dissertations (ETD). Paper 467. http://dx.doi.org/10.21007/etd.cghs.2018.0472. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. The umorT Microenvironment Regulates Retinoblastoma Cell Survival Document Type Dissertation Degree Name Doctor of Philosophy (PhD) Program Biomedical Sciences Track Neurosciences Research Advisor Monica M. Jablonski, Ph.D. Committee Vanessa M. Morales-Tirado, M.S., Ph.D. Lawrence M. Pfeffer, Ph.D. Anton J. Reiner, Ph.D. Matthew W. Wilson, M.D. ORCID http://orcid.org/0000-0002-7393-733 DOI 10.21007/etd.cghs.2018.0472 This dissertation is available at UTHSC Digital Commons: https://dc.uthsc.edu/dissertations/467 The Tumor Microenvironment Regulates Retinoblastoma Cell Survival A Dissertation Presented for The Graduate Studies Council The University of Tennessee Health Science Center In Partial Fulfillment Of the Requirements for the Degree Doctor of Philosophy From The University of Tennessee By Zachary K.