DOCSLIB.ORG

OLR1 Promotes Pancreatic Cancer Metastasis Via Increased C-Myc

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
OLR1 Promotes Pancreatic Cancer Metastasis Via Increased C-Myc Published OnlineFirst February 4, 2020; DOI: 10.1158/1541-7786.MCR-19-0718 MOLECULAR CANCER RESEARCH | CANCER GENES AND NETWORKS OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2 A C Gang Yang1, Guangbing Xiong1,2, Mengyu Feng1, Fangyu Zhao1, Jiangdong Qiu1, Yueze Liu1, Zhe Cao1, Huanyu Wang1, Jinshou Yang1, Lei You1, Lianfang Zheng3, Taiping Zhang1,4, and Yupei Zhao1 ABSTRACT ◥ Pancreatic cancer is one of the most lethal human malignancies, pancreatic cancer cells in vitro and in vivo. Mechanistically, partly because of its propensity for metastasis. However, the OLR1 increased HMGA2 transcription by upregulating c-Myc mechanisms of metastasis in pancreatic cancer remain unclear. expression to promote the metastasis of pancreatic cancer cells. In Oxidized low-density lipoprotein receptor 1 (OLR1), a lectin-like addition, patients with pancreatic cancer with high expression of scavenger receptor that recognizes several ligands, such as oxidized OLR1–c-Myc–HMGA2 axis showed worse prognosis compared low-density lipoprotein, was previously reported in cardiovascular with patients with low expression of OLR1–c-Myc–HMGA2 axis. and metabolic diseases. The role and mechanism of OLR1 in pancreatic cancer is unclear. In this study, we found that OLR1 Implications: Our findings suggested that the OLR1–c-Myc– expression was significantly higher in pancreatic cancer tissues than HMGA2 axis promotes metastasis of pancreatic cancer cells and that in adjacent normal tissues and closely associated with reduced may serve as potential therapeutic targets and prognosis markers for overall survival. OLR1 promoted proliferation and metastasis of patients with pancreatic cancer. Introduction Oxidized low-density lipoprotein receptor 1 (OLR1) is a lectin-like scavenger receptor that recognizes several ligands, such as oxidized Pancreatic cancer is the fourth and sixth leading cause of cancer- low-density lipoprotein, polyanionic chemicals, and anionic phospho- related death in the United States and China, respectively, with an lipids (5). OLR1 is mainly distributed in vascular endothelial cells and overall survival (OS) rate of less than 9% in both countries (1, 2). tissues with abundant blood vessels such as renal, pulmonary, and Furthermore, the mortality rate of pancreatic cancer is increasing, and neuronal tissues. Previous studies on OLR1 mainly focused on its role pancreatic cancer is projected to be the second most common cause of in cardiovascular and metabolic diseases, such as atherosclerosis, cancer-related death by 2030 in the United States (3). Because of the hypertension, diabetes, and hyperlipemia (6–8). Upregulation of atypical clinical symptoms of pancreatic cancer, the majority of ORL1 in cardiovascular and metabolic diseases increased DNA dam- patients already show metastases at diagnosis and thus are unable to age caused by intracellular reactive oxygen species, promoted the be treated by radical operation (4). Despite treatment with surgical release of inflammatory cytokines, and enhanced hypoxia and angio- resection, most patients with pancreatic cancer eventually develop genesis (5, 9). Notably, these processes are also closely related to cancer metastases because of recurrence or chemoresistance. The current development (10). Indeed, upregulation of OLR1 was recently found in understanding of the underlying mechanism of metastasis in pancre- multiple cancers and shown to be involved in tumorigenesis, cancer atic cancer remains limited. Therefore, clarifying the metastasis development, and metastasis (11–14). For example, activation of the mechanisms is important for developing new treatment strategies for TNFa/NF-kB pathway upregulates OLR1 to promote the migration of pancreatic cancer and prolonging patient survival. breast cancer cells (11, 15). In return, upregulated OLR1 also activates NF-kB signaling to induce cellular transformation in breast cancer and 1Department of General Surgery, Peking Union Medical College Hospital, Chinese trigger epithelial–mesenchymal transition (EMT) to induce metastasis Academy of Medical Sciences and Peking Union Medical College, Beijing, China. in prostate cancer (13, 16). OLR1 also facilitates metastasis of gastric 2Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji cancer through driving PI3K/Akt/GSK3b activation (17). Recently, Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 3 our group found that OLR1 was upregulated by lncRNA GSTM3TV2 Province, China. Department of Nuclear Medicine, Peking Union Medical Col- through competitively sponging let-7 to promote gemcitabine resis- lege Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 4Clinical Immunology Center, Chinese Academy of tance in pancreatic cancer (18). Together these studies suggest that Medical Sciences and Peking Union Medical College, Beijing, China. OLR1 may be a link between metabolic diseases and cancer. However, the role of OLR1 in pancreatic cancer has not been completely Note: Supplementary data for this article are available at Molecular Cancer Research Online (http://mcr.aacrjournals.org/). revealed. The proto-oncogene c-Myc regulates DNA synthesis, cellular pro- Corrected online June 17, 2021. liferation, differentiation, survival, and immortalization through its Corresponding Authors: Yupei Zhao, Peking Union Medical College Hospital, function as a transcription factor that binds canonical DNA-binding Chinese Academy of Medical Sciences, 1# Shuai Fu Yuan Hu Tong, Beijing motifs (E box 50-CACGTG-30) in the promoters of target genes to 100730, China. Phone: 008-669-156-007; Fax: 008-669-156-007; E-mail: [email protected]; and Taiping Zhang, [email protected] regulate gene expression. c-Myc plays an important role in the initiation and development of cancer by its placement at the crossroads Mol Cancer Res 2020;18:685–97 of many cancer-related signaling pathways (19, 20). c-Myc promotes doi: 10.1158/1541-7786.MCR-19-0718 cell metastasis in many cancers and is regulated by many factors (19). Ó2020 American Association for Cancer Research. However, the relationship between OLR1 and c-Myc is unclear. AACRJournals.org | 685 Downloaded from mcr.aacrjournals.org on September 30, 2021. © 2020 American Association for Cancer Research. Published OnlineFirst February 4, 2020; DOI: 10.1158/1541-7786.MCR-19-0718 Yang et al. High mobility group AT-hook 2 (HMGA2), a member of high Western blot analysis mobility group A, plays a critical role in growth during embryonic Western blot analysis was performed as described previously (28). development but is expressed at low levels in adult tissues (21). Briefly, protein lysates (20 mg) were separated using SDS-PAGE, and However, HMGA2 has been reported to be upregulated in many primary and secondary antibodies were applied to detect target cancers (21–23). HMGA2 mainly functions as a transcription cor- proteins. An enhanced chemiluminescence assay was used to visualize egulator by modifying chromosomal architecture or recruiting other protein bands. Primary antibodies targeting OLR1 and HMGA2 were transcription-associated proteins to regulate the differentiation and purchased from Proteintech Group and c-Myc and b-actin antibodies proliferation of cells (24). HMGA2 was recently shown to promote were obtained from Cell Signaling Technology. metastasis in cancer by regulating EMT and enhancing TGFb signaling (21–23, 25). qRT-PCR In this study, we investigated the role and potential function of TRizol reagent (Invitrogen) was used for the extraction of total OLR1 in pancreatic cancer. We found that OLR1 expression was RNA and cDNA synthesis was performed using the Takara First highly expressed in pancreatic cancer tissues and that OLR1 pro- Strand cDNA Synthesis Kit following the manufacturer's instruc- moted metastasis of pancreatic cancer cells through increasing tions. qRT-PCR assays were performed independently at least three transcription of HMGA2 through c-Myc. Our results identified a times. The PCR primers are listed in the Supplementary Materials novel OLR1-c-Myc-HMGA2 axis and show its potential as a and Methods. combined biomarker of pancreatic cancer patient prognosis. RNA-sequencing and data analysis A RNeasy MINI KIT (Qiagen) was used for the extraction of Materials and Methods total RNA. The directional (stranded) libraries were generated Cell lines and clinical specimens using an Illumina platform for the paired-end sequencing of The human pancreatic cancer cell lines Bxpc-3 and Mia PaCa-2 Bxpc-3 cells. Cuffdiff was used to obtain the sequence count data were purchased from the ATCC and cultured in DMEM or RPMI1640 [fragments per kilobase of transcript per million mapped reads with 10% FBS (HyClone) in a 5% CO2 cell culture incubator at 37 C. (FPKM) values] to conduct differential expression analysis. Shang- All cell lines were authenticated using high-resolution small tandem hai Biotechnology Corporation performed the library construction repeats (STR) profiling at Department of General Surgery Laboratory. and sequencing. The mycoplasma of cells was examined by MycoSensor PCR Assay Kit (Catalog No. C0301S; Beyotime). Cells were grown for 15 passages and Chromatin immunoprecipitation assay then replaced with fresh stocks. The 99 clinical pancreatic cancer Chromatin immunoprecipitation (ChIP) assays were performed specimens were obtained from patients who received surgery in the using a ChIP Assay Kit (Millipore, 17-295) according
Load more

Recommended publications
  • Polymorphisms with Late-Onset Alzheimer Disease in Han Chinese
    172 Original Article on Translational Neurodegeneration Page 1 of 8 Association of lectin-like oxidized low density lipoprotein receptor 1 (OLR1) polymorphisms with late-onset Alzheimer disease in Han Chinese Zuo-Teng Wang1#, Xiao-Ling Zhong2#, Meng-Shan Tan1, Hui-Fu Wang1, Chen-Chen Tan1, Wei Zhang1, Zhan-Jie Zheng3, Ling-Li Kong3, Lan Tan1, Li Sun2 1Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, China; 2Department of Neurology, Qingdao Central Hospital, Qingdao University, Qingdao 266042, China; 3Department of Geriatric, Qingdao Mental Health Center, Qingdao 266034, China Contributions: (I) Conception and design: All authors; (II) Administrative support: All authors; (III) Provision of study materials or patients: All authors; (VI) Collection and assembly of data: All authors; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. #These authors should be regarded as co-first authors. Correspondence to: Dr. Lan Tan, MD, PhD. Department of Neurology, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao 266071, China. Email: [email protected]; Dr. Li Sun, MD, PhD. Department of Neurology, Qingdao Central Hospital, Qingdao University, Qingdao 266042, China. Email: [email protected]. Background: Lectin-like oxidized low density lipoprotein receptor 1 (OLR1) locates within the area of chromosome 12p, which has been identified as the AD-susceptible region, and plays a role in lipid metabolism. Therefore, it has been suggested to be a good candidate gene for Alzheimer’s disease (AD). Several SNPs within OLR1 have been reported to have association with AD among Caucasians. Methods: We selected and genotyped three SNPs (rs1050283, rs1050286, rs17808009) in OLR1 to investigate its possible relationship with the onset of late-onset Alzheimer disease(LOAD) in 984 LOAD cases and 1,354 healthy controls among northern Han Chinese.
    [Show full text]
  • Genome Wide Analysis of TLR1/2- and TLR4-Activated SZ95 Sebocytes
    RESEARCH ARTICLE Genome wide analysis of TLR1/2- and TLR4- activated SZ95 sebocytes reveals a complex immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands DaÂniel ToÈ rőcsik1,2*, DoÂra KovaÂcs1, SzilaÂrd PoÂliska3, Zita Szentkereszty-KovaÂcs1, a1111111111 Marianna LovaÂszi1, Katalin Hegyi1, Andrea Szegedi1,4, Christos C. Zouboulis5, a1111111111 Mona Ståhle2 a1111111111 a1111111111 1 Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 2 Unit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, a1111111111 Stockholm, Sweden, 3 Department of Biochemistry and Molecular Biology, Genomic Medicine and Bioinformatics Core Facility, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 4 Division of Dermatological Allergology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary, 5 Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodore Fontane, Dessau, Germany OPEN ACCESS * [email protected] Citation: ToÈrőcsik D, KovaÂcs D, PoÂliska S, Szentkereszty-KovaÂcs Z, LovaÂszi M, Hegyi K, et al. (2018) Genome wide analysis of TLR1/2- and TLR4-activated SZ95 sebocytes reveals a complex Abstract immune-competence and identifies serum amyloid A as a marker for activated sebaceous glands. Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in PLoS ONE 13(6): e0198323. https://doi.org/ the development of acne. Still, there is only limited knowledge on their effect on sebocytes. 10.1371/journal.pone.0198323 In this work we performed global gene expression profile analysis with functional clustering Editor: Mauro Picardo, San Gallicano Dermatologic of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide Institute, ITALY [LPS])-activated SZ95 sebocytes.
    [Show full text]
  • Basic Science * Drug X Is Used for Ongoing IP/Patent Assessment Heart: First Published As 10.1136/Heartjnl-2021-BCS.199 on 4 June 2021
    Abstracts Basic science * Drug X is used for ongoing IP/patent assessment Heart: first published as 10.1136/heartjnl-2021-BCS.199 on 4 June 2021. Downloaded from Conflict of Interest No BS1 REPROGRAMMING HUMAN MACROPHAGES WITH DRUG X: POTENTIAL MECHANISMS FOR STABILISATION OF ATHEROSCLEROTIC PLAQUES BS2 MECHANOSENSOR PIEZO1 IN SKELETAL MUSCLE PERICYTES 1Klaudia Kocsy, 1Endre Kiss-Toth, 2Jessica Redgrave, 2Arshad Majid, 3Sheila Francis. 1Department of Infection, Immunity & Cardiovascular Disease, The University of Sheffield, 1Yilizila Abudushalamu, 1Hema Viswambharan, 2Romana Mughal, 1Richard Cubbon, Sheffield, UK; 2Department of Neuroscience, The University of Sheffield, Sheffield, UK; 3The 1Mark Kearney, 1David Beech, 1Piruthivi Sukumar. 1Discovery and Translational Science University of Sheffield, Sheffield, UK Department Leeds Institute of Cardiovascular and Metabolic Medic, Leeds, UK; 2Department of Optometry and Vision Sciences School of Applied Sciences University of Huddersfield 10.1136/heartjnl-2021-BCS.199 10.1136/heartjnl-2021-BCS.200 Introduction Ischemic stroke is commonly caused by large artery atherosclerosis. Patients with a high atherosclerotic bur- Introduction Pericytes (PC) are mural cells which are present den (stenosis) and inflamed or ulcerated plaque are at in blood microvessels. They play an important part in the for- increased risk of early recurrent ischaemic events. Treatment mation and stabilization of new blood vessels. They are essen- with anti-inflammatory agents may therefore reduce stroke tial for vascular development and cardiovascular homeostasis. incidence and recurrence in patients with this condition, but They wrap around the endothelial cells (EC) and endothelial- in vitro human studies of the possible mechanisms are lacking. pericyte communication is both via physical contact and para- 1 We hypothesised that an anti-inflammatory compound crine signalling.
    [Show full text]
  • Evaluating the Effect of TLR4-Overexpressing on The
    Guo et al. J of Biol Res-Thessaloniki (2020) 27:13 https://doi.org/10.1186/s40709-020-00124-3 Journal of Biological Research-Thessaloniki RESEARCH Open Access Evaluating the efect of TLR4-overexpressing on the transcriptome profle in ovine peripheral blood mononuclear cells Xiaofei Guo1†, Jinlong Zhang1,2†, Yao Li2, Jing Yang1, Yihai Li1, Chunxiao Dong1, Guoshi Liu2, Zhengxing Lian2 and Xiaosheng Zhang1* Abstract Background: Toll-like receptor 4 (TLR4) plays an important role in the elimination of Gram-negative bacteria infec- tions and the initiation of antiinfammatory response. Using the technology of pronuclear microinjection, genetically modifed (GM) sheep with TLR4 overexpression were generated. Previous studies have shown that these GM sheep exhibited a higher infammatory response to Gram-negative bacteria infection than wild type (WT) sheep. In order to evaluate the gene expression of GM sheep and study the co-expressed and downstream genes for TLR4, peripheral blood mononuclear cells (PBMC) from TLR4-overexpressing (Tg) and wild type (WT) sheep were selected to discover the transcriptomic diferences using RNA-Seq. Result: An average of 18,754 and 19,530 known genes were identifed in the Tg and WT libraries, respectively. A total of 338 known genes and 85 novel transcripts were found to be diferentially expressed in the two libraries (p < 0.01). A diferentially expressed genes (DEGs) enrichment analysis showed that the GO terms of infammatory response, cell recognition, etc. were signifcantly (FDR < 0.05) enriched. Furthermore, the above DEGs were signifcantly (FDR < 0.05) enriched in the sole KEGG pathway of the Phagosome. Real-time PCR showed the OLR1, TLR4 and CD14 genes to be diferentially expressed in the two groups, which validated the DEGs data.
    [Show full text]
  • Modulation of Cell-Mediated Immunity by HIV-1 Infection of Macrophages
    Modulation of cell-mediated immunity by HIV-1 infection of macrophages Lucy Caitríona Kiernan Bell Division of Infection and Immunity University College London PhD Supervisor: Dr Mahdad Noursadeghi A thesis submitted for the degree of Doctor of Philosophy University College London August 2014 Declaration I, Lucy Caitríona Kiernan Bell, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Abstract Cell-mediated immunity (CMI) is central to the host response to intracellular pathogens such as Mycobacterium tuberculosis (Mtb). The function of CMI can be modulated by human immunodeficiency virus (HIV)-1 via its pleiotropic effects on the immune response, including modulation of macrophages, which are parasitized by both HIV-1 and Mtb. HIV-1 infection is associated with increased risk of tuberculosis (TB), and so in this thesis I sought to explore the host/pathogen interactions through which HIV-1 dysregulates CMI, and thus changes the natural history of TB. Using an in vitro model of human monocyte-derived macrophages (MDMs), I characterise a phenotype wherein HIV-1 specifically attenuates production of the immunoregulatory cytokine interleukin (IL)-10 in response to Mtb and other innate immune stimuli. I show that this phenotype requires HIV-1 integration and gene expression, and may result from a function of the HIV-1 accessory proteins. I identify that the phosphoinositide 3-kinase (PI3K) pathway specifically regulates IL-10 production in human MDMs, and thus may be a target for HIV-1 to mediate IL-10 attenuation.
    [Show full text]
  • Critical Role of Oxidized LDL Receptor-1 in Intravascular
    www.nature.com/scientificreports OPEN Critical role of oxidized LDL receptor‑1 in intravascular thrombosis in a severe infuenza mouse model Marumi Ohno1, Akemi Kakino2, Toshiki Sekiya1, Naoki Nomura1, Masashi Shingai1, Tatsuya Sawamura2 & Hiroshi Kida1* Although coagulation abnormalities, including microvascular thrombosis, are thought to contribute to tissue injury and single‑ or multiple‑organ dysfunction in severe infuenza, the detailed mechanisms have yet been clarifed. This study evaluated infuenza‑associated abnormal blood coagulation utilizing a severe infuenza mouse model. After infecting C57BL/6 male mice with intranasal applications of 500 plaque‑forming units of infuenza virus A/Puerto Rico/8/34 (H1N1; PR8), an elevated serum level of prothrombin fragment 1 + 2, an indicator for activated thrombin generation, was observed. Also, an increased gene expression of oxidized low‑density lipoprotein (LDL) receptor‑1 (Olr1), a key molecule in endothelial dysfunction in the progression of atherosclerosis, was detected in the aorta of infected mice. Body weight decrease, serum levels of cytokines and chemokines, viral load, and infammation in the lungs of infected animals were similar between wild‑type and Olr1 knockout (KO) mice. In contrast, the elevation of prothrombin fragment 1 + 2 levels in the sera and intravascular thrombosis in the lungs by PR8 virus infection were not induced in KO mice. Collectively, the results indicated that OLR1 is a critical host factor in intravascular thrombosis as a pathogeny of severe infuenza. Thus, OLR1 is a promising novel therapeutic target for thrombosis during severe infuenza. Infuenza is a respiratory disease and remains a major health concern, causing approximately half a million deaths per year globally1.
    [Show full text]
  • TDP43 Exacerbates Atherosclerosis Progression by Promoting Inflammation and Lipid Uptake of Macrophages
    fcell-09-687169 July 2, 2021 Time: 12:55 # 1 ORIGINAL RESEARCH published: 05 July 2021 doi: 10.3389/fcell.2021.687169 TDP43 Exacerbates Atherosclerosis Progression by Promoting Inflammation and Lipid Uptake of Macrophages Ning Huangfu, Yong Wang, Zhenyu Xu, Wenyuan Zheng, Chunlan Tao, Zhenwei Li, Yewen Hu and Xiaomin Chen* Department of Cardiology, Ningbo First Hospital, Ningbo, China Objective: Atherosclerosis (AS), characterized by cholesterol overloaded-macrophages accumulation and plaque formation in blood vessels, is the major cause of cardiovascular disease. Transactive response DNA-binding protein∼43 kDa (TDP43) has recently been identified as an independent driver of neurodegenerative diseases Edited by: through triggering inflammatory response. This study investigated whether TDP43 is Yuxain Shen, involved in AS development, especially in macrophages-mediated-foam cell formation Anhui Medical University, China and inflammatory responses. Reviewed by: Juntang Shao, Methods: Transactive response DNA-binding protein∼43 kDa expressions in Anhui Medical University, China Heiko Lemcke, oxidized low-density lipoprotein (oxLDL)-treated macrophages and peripheral blood University Medical Center Rostock, mononuclear cells (PBMCs) from patients with coronary artery disease (CAD) were Germany detected by real time-polymerase chain reaction (RT-PCR), Western blot, and *Correspondence: immunofluorescence. Gene gain or loss of function was used to investigate the effects Xiaomin Chen [email protected] of TDP43 on macrophages-mediated lipid untake and inflammation with ELISA, protein immunoprecipitation, RT-PCR, Western blot, and immunofluorescence. Macrophage Specialty section: TDP43 specific knockout mice with ApoE−=− background were fed with western This article was submitted to Signaling, diet for 12 weeks to establish AS model, and used to explore the role of TDP43 a section of the journal on AS progression.
    [Show full text]
  • SARS-Cov-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-Like Receptors in Pathogenesis
    International Journal of Molecular Sciences Article SARS-CoV-2 Infected Pediatric Cerebral Cortical Neurons: Transcriptomic Analysis and Potential Role of Toll-like Receptors in Pathogenesis Agnese Gugliandolo 1 , Luigi Chiricosta 1 , Valeria Calcaterra 2,3,† , Mara Biasin 4 , Gioia Cappelletti 4 , Stephana Carelli 5 , Gianvincenzo Zuccotti 2,4, Maria Antonietta Avanzini 6 , Placido Bramanti 1, Gloria Pelizzo 4,7 and Emanuela Mazzon 1,*,† 1 IRCCS Centro Neurolesi “Bonino-Pulejo”, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy; [email protected] (A.G.); [email protected] (L.C.); [email protected] (P.B.) 2 Department of Pediatrics, Ospedale dei Bambini “Vittore Buzzi”, 20154 Milano, Italy; [email protected] (V.C.); [email protected] (G.Z.) 3 Pediatrics and Adolescentology Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy 4 Department of Biomedical and Clinical Sciences–L. Sacco, University of Milan, 20157 Milan, Italy; [email protected] (M.B.); [email protected] (G.C.); [email protected] (G.P.) 5 Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy; [email protected] 6 Cell Factory, Pediatric Hematology Oncology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; [email protected] 7 Pediatric Surgery Unit, Ospedale dei Bambini “Vittore Buzzi”, 20154 Milano, Italy Citation: Gugliandolo, A.; Chiricosta, * Correspondence: [email protected] L.; Calcaterra, V.; Biasin, M.; † These authors contribute equally to the paper as senior author. Cappelletti, G.; Carelli, S.; Zuccotti, G.; Avanzini, M.A.; Bramanti, P.; Abstract: Different mechanisms were proposed as responsible for COVID-19 neurological symptoms Pelizzo, G.; et al.
    [Show full text]
  • Upregulation of OLR1 and IL17A Genes and Their Association with Blood Glucose and Lipid Levels in Femoropopliteal Artery Disease
    1160 EXPERIMENTAL AND THERAPEUTIC MEDICINE 13: 1160-1168, 2017 Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease CANER ARSLAN1*, BURCU BAYOGLU2*, CIGDEM TEL1, MUJGAN CENGIZ2, AHMET DIRICAN3 and KAZIM BESIRLI1 Departments of 1Cardiovascular Surgery and 2Medical Biology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34098; 3Department of Biostatistics and Medical Informatics, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey Received April 4, 2016; Accepted October 28, 2016 DOI: 10.3892/etm.2017.4081 Abstract. Oxidized low-density lipoprotein receptor 1 (OLR1) identify an association between OLR1 and IL17A genes and and interleukin 17A (IL17A) have pro‑inflammatory roles in FP artery disease. OLR1 and IL17A mRNA transcripts may be the development of cardiovascular disorders. The present associated with blood lipid parameters and with the develop- study evaluated the association of OLR1 and IL17A and their ment of FP artery disease. polymorphisms with the development of femoropopliteal (FP) artery disease. The mRNA expression of OLR1 and Introduction IL17A in peripheral blood mononuclear cells as well as the frequency of OLR1 rs11053646 and IL17A rs8193037 and Peripheral artery disease (PAD) is an occlusive disease of rs3819025 polymorphisms were assessed by polymerase the peripheral circulation system. PAD is one of the major chain reaction in 70 patients with FP artery disease and syndromes of atherothrombosis and is found in 15‑20% of 80 age‑matched disease‑free controls. Furthermore, the levels individuals aged >70 years (1). Early diagnosis is important of plasma cytokines were assessed by multiplex immunoassay. to improve patient quality of life and prevent secondary OLR1 and IL17A mRNA expression was significantly higher vascular events, such as stroke or acute myocardial infarc- in patients with FP artery disease compared with that in tion (AMI) (2).
    [Show full text]
  • Recombinant Human LOX-1/OLR1 Catalog Number: 1798-LX
    Recombinant Human LOX-1/OLR1 Catalog Number: 1798-LX DESCRIPTION Source Mouse myeloma cell line, NS0­derived Ser61­Gln273, with an N­terminal 9­His tag Accession # P78380 N­terminal Sequence His Analysis Structure / Form Disulfide­linked homodimer Predicted Molecular 25.5 kDa (monomer) Mass SPECIFICATIONS SDS­PAGE 35­40 kDa, reducing conditions Activity Measured by its binding ability in a functional ELISA. Immobilized rhLOX­1 at 5 µg/mL (100 µL/well) can bind biotinylated advanced glycation endproducts of bovine serum albumin (AGE­BSA) with a linear range of 0.02­1 µg/mL. Endotoxin Level <0.10 EU per 1 μg of the protein by the LAL method. Purity >95%, by SDS­PAGE under reducing conditions and visualized by silver stain. Formulation Lyophilized from a 0.2 μm filtered solution in PBS with Trehalose. See Certificate of Analysis for details. PREPARATION AND STORAGE Reconstitution Reconstitute at 100 μg/mL in sterile PBS. Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. Stability & Storage Use a manual defrost freezer and avoid repeated freeze­thaw cycles. l 12 months from date of receipt, ­20 to ­70 °C as supplied. l 1 month, 2 to 8 °C under sterile conditions after reconstitution. l 3 months, ­20 to ­70 °C under sterile conditions after reconstitution. BACKGROUND Lectin­like oxidized low­density­lipoprotein receptor­1 (LOX­1), also known as oxidized low­density­lipoprotein receptor­1 (OLR­1), is a type II transmembrane receptor belonging to the C­type lectin family (1). It also belongs to the functionally defined scavenger receptor (SR) superfamily, whose members share the common ability to bind and internalize modified forms of Low Density Lipoproteins (LDL) (2 ­ 4).
    [Show full text]
  • Nomenclature Standardizing Scavenger Receptor
    Standardizing Scavenger Receptor Nomenclature Mercy PrabhuDas, Dawn Bowdish, Kurt Drickamer, Maria This information is current as Febbraio, Joachim Herz, Lester Kobzik, Monty Krieger, of April 20, 2014. John Loike, Terry K. Means, Soren K. Moestrup, Steven Post, Tatsuya Sawamura, Samuel Silverstein, Xiang-Yang Wang and Joseph El Khoury Downloaded from J Immunol 2014; 192:1997-2006; ; doi: 10.4049/jimmunol.1490003 http://www.jimmunol.org/content/192/5/1997 http://www.jimmunol.org/ References This article cites 76 articles, 39 of which you can access for free at: http://www.jimmunol.org/content/192/5/1997.full#ref-list-1 Subscriptions Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscriptions Permissions Submit copyright permission requests at: http://www.aai.org/ji/copyright.html at McMaster Univ Hlth Sci Lib on April 20, 2014 Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/cgi/alerts/etoc The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 9650 Rockville Pike, Bethesda, MD 20814-3994. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Standardizing Scavenger Receptor Nomenclature x Mercy PrabhuDas,* Dawn Bowdish,† Kurt Drickamer,‡ Maria Febbraio, { ‖ # †† Joachim Herz, Lester Kobzik, Montyxx Krieger, John Loike,**{{ Terry K. Means,‖‖ Soren K. Moestrup,‡‡ Steven Post, Tatsuya Sawamura, Samuel Silverstein, Xiang-Yang Wang,## and Joseph El Khoury*** Scavenger receptors constitute a large family of proteins at the workshop and to solicit additional feedback that are structurally diverse and participate in a wide from the broader research community.
    [Show full text]
  • Suppressor Cells in Cancer Patients Polymorphonuclear Myeloid
    SCIENCE IMMUNOLOGY | RESEARCH ARTICLE CANCER 2016 © The Authors, some rights reserved; Lectin-type oxidized LDL receptor-1 distinguishes exclusive licensee American Association population of human polymorphonuclear for the Advancement of Science. myeloid-derived suppressor cells in cancer patients Thomas Condamine,1* George A. Dominguez,1 Je-In Youn,1† Andrew V. Kossenkov,1 Sridevi Mony,1 Kevin Alicea-Torres,1 Evgenii Tcyganov,1 Ayumi Hashimoto,1 Yulia Nefedova,1 Cindy Lin,1 Simona Partlova,1‡ Alfred Garfall,2,3 Dan T. Vogl,2,3 Xiaowei Xu,2 Stella C. Knight,4 George Malietzis,4,5 Gui Han Lee,4,5 Evgeniy Eruslanov,2 Steven M. Albelda,2,3 Xianwei Wang,6 Jawahar L. Mehta,6 Meenakshi Bewtra,3 Anil Rustgi,2,3 Neil Hockstein,7 Robert Witt,7 Gregory Masters,7 Brian Nam,7 Denis Smirnov,8 Manuel A. Sepulveda,8 Dmitry I. Gabrilovich1§ Downloaded from Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are important regulators of immune re- sponses in cancer and have been directly implicated in the promotion of tumor progression. However, the heter- ogeneity of these cells and the lack of distinct markers hamper the progress in understanding the biology and clinical importance of these cells. Using partial enrichment of PMN-MDSC with gradient centrifugation, we determined that low-density PMN-MDSC and high-density neutrophils from the same cancer patients had a distinct gene profile. The most prominent changes were observed in the expression of genes associated with endoplasmic http://immunology.sciencemag.org/ reticulum (ER) stress. Unexpectedly, low-density lipoprotein (LDL) was one of the most increased regulators, and its receptor oxidized LDL receptor 1 (OLR1) was one of the most overexpressed genes in PMN-MDSC.
    [Show full text]