DOCSLIB.ORG

Recombinant Mouse Lymphotoxin Α1/Β2 Catalog Number: 9968-LY/CF

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recombinant Mouse Lymphotoxin Α1/Β2 Catalog Number: 9968-LY/CF Recombinant Mouse Lymphotoxin α1/β2 Catalog Number: 9968-LY/CF DESCRIPTION Source Mouse myeloma cell line, NS0­derived mouse Lymphotoxin protein Mouse LT alpha Mouse LT beta Mouse LT beta (Lys59­Leu202) GGGGS (Leu153­Gly306) GGGGS (Leu153­Gly306) Accession # P09225 Accession # P41155 Accession # P41155 N­terminal Sequence Lys59 Analysis Structure / Form GS­linked heterotrimer Predicted Molecular 50 kDa Mass SPECIFICATIONS SDS­PAGE 42­63 kDa, reducing conditions Activity Measured in a cell proliferation assay using NIH­3T3 mouse embryonic fibroblast cells. The ED50 for this effect is 0.3­2.1 ng/mL Endotoxin Level <0.10 EU per 1 μg of the protein by the LAL method. Purity >95%, by SDS­PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining. Formulation Lyophilized from a 0.2 μm filtered solution in PBS. See Certificate of Analysis for details. PREPARATION AND STORAGE Reconstitution Reconstitute at 500 μg/mL in PBS. Shipping The product is shipped at ambient temperature. Upon receipt, store it immediately at the temperature recommended below. Stability & Storage l 12 months from date of receipt, ≤ ­20 °C as supplied. l 1 month, 2 to 8 °C under sterile conditions after reconstitution. l 3 months, ≤ ­20 °C under sterile conditions after reconstitution. DATA Bioactivity SDS­PAGE Recombinant Mouse 2 μg/lane of Recombinant Mouse Lymphotoxin alpha1/beta2 Lymphotoxin α1/β2 was resolved with SDS­PAGE under reducing (R) and non­ (Catalog # 9968­ reducing (NR) conditions and visualized by Coomassie® blue LY/CF) induces NIH­ staining, showing bands at 42­63 kDa. 3T3 mouse embryonic fibroblast cell proliferation. The ED50 for this effect is 0.3­2.1 ng/mL. Rev. 6/26/2018 Page 1 of 2 Recombinant Mouse Lymphotoxin α1/β2 Catalog Number: 9968-LY/CF BACKGROUND Lymphotoxin alpha (LT alpha) and Lymphotoxin beta (LT beta) are pro­inflammatory TNF superfamily ligands that play important roles in immune system development (1, 2). Mouse LT alpha cDNA encodes a 202 amino acid (aa) secreted soluble protein with a 33 aa signal sequence. The mature mouse LT alpha shares 75% aa sequence identity with human LT alpha (3, 4). Mouse LT beta cDNA encodes a 306 aa type II membrane protein with a 27 aa N­terminal cytoplasmic domain, a 21 aa transmembrane region, and a 258 aa extracellular domain. It shares 73% aa sequence identity with human LT beta within common regions of their extracellular domains (5). Secreted LT alpha assembles as a soluble homotrimer, LT alpha 3. In addition, secreted LT alpha also complexes with the membrane associated LT beta to generate two types of heterotrimers, LT alpha 1/beta 2 and LT alpha 2/beta 1 (5). The soluble LT alpha 3 binds both TNF RI (p55) and TNF RII (p75). In contrast, the predominant membrane­bound heterotrimer, LT alpha 1/beta 2, binds only to the lymphotoxin beta receptor (LT beta R). LT alpha 2/beta 1 is capable of binding LT beta R, TNF RI (p55), and TNF RII (p75). LT plays a role in normal lymphoid organogenesis (6, 7). The LT alpha 1/beta 2 heterotrimer binds and activates the LT beta R/TNFRSF3 (LT beta R) which is expressed on macrophages, dendritic cells, hepatocytes, intestinal epithelial cells (IEC), follicular dendritic cells (FDC), and high endothelial venules (HEV) (2, 8, 9). LT beta R also serves as a receptor for LIGHT/TNFSF14 (10). LT alpha 1/beta 2 promotes the development of FDC networks and HEV in lymphoid tissue, the class switching of immature B cells for IgA production, and the production of homeostatic IL­22 by ILCs (11­14). It can be shed by ADAM17 or MMP­8 mediated cleavage, and the released heterotrimer circulates in the serum and is elevated in synovial fluid of rheumatoid arthritis patients (15). References: 1. Lu, T.T. and J.L. Browning (2014) Front. Immunol. 5:47. 2. Upadhyay, V. and Y.­X. Fu (2014) Cytokine Growth Factor Rev. 25:227. 3. Gray, P.W. et al. (1984) Nature 312:721. 4. Nedwin, G.E. et al. (1985) J. Cell Biochem. 29:171. 5. Browning, J.L. et al. (1993) Cell 72:847. 6. Ettinger R. et al. (1996) Proc. Natl. Acad. Sci. USA 93:13102. 7. Cuff, C.A. et al. (1998) J. Immunol. 161:6853. 8. Sudhamsu, J. et al. (2013) Proc. Natl. Acad. Sci. USA 110:19896. 9. Crowe, P.D. et al. (1994) Science 264:707. 10. Eldredge, J. et al. (2006) Biochemistry 45:10117. 11. Kruglov, A.A. et al. (2013) Science 342:1243. 12. Futterer, A. et al. (1998) Immunity 9:59. 13. Koni, P.A. et al. (1997) Immunity 6:491. 14. Ota, N. et al. (2011) Nat. Immunol. 12:941. 15. Young, J. et al. (2010) Cytokine 51:78. Rev. 6/26/2018 Page 2 of 2 .
Load more

Recommended publications
  • TNF Decoy Receptors Encoded by Poxviruses
    pathogens Review TNF Decoy Receptors Encoded by Poxviruses Francisco Javier Alvarez-de Miranda † , Isabel Alonso-Sánchez † , Antonio Alcamí and Bruno Hernaez * Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Campus de Cantoblanco, Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain; [email protected] (F.J.A.-d.M.); [email protected] (I.A.-S.); [email protected] (A.A.) * Correspondence: [email protected]; Tel.: +34-911-196-4590 † These authors contributed equally. Abstract: Tumour necrosis factor (TNF) is an inflammatory cytokine produced in response to viral infections that promotes the recruitment and activation of leukocytes to sites of infection. This TNF- based host response is essential to limit virus spreading, thus poxviruses have evolutionarily adopted diverse molecular mechanisms to counteract TNF antiviral action. These include the expression of poxvirus-encoded soluble receptors or proteins able to bind and neutralize TNF and other members of the TNF ligand superfamily, acting as decoy receptors. This article reviews in detail the various TNF decoy receptors identified to date in the genomes from different poxvirus species, with a special focus on their impact on poxvirus pathogenesis and their potential use as therapeutic molecules. Keywords: poxvirus; immune evasion; tumour necrosis factor; tumour necrosis factor receptors; lymphotoxin; inflammation; cytokines; secreted decoy receptors; vaccinia virus; ectromelia virus; cowpox virus Citation: Alvarez-de Miranda, F.J.; Alonso-Sánchez, I.; Alcamí, A.; 1. TNF Biology Hernaez, B. TNF Decoy Receptors TNF is a potent pro-inflammatory cytokine with a broad range of biological effects, Encoded by Poxviruses. Pathogens ranging from the activation of inflammatory gene programs to cell differentiation or 2021, 10, 1065.
    [Show full text]
  • Dimerization of Ltβr by Ltα1β2 Is Necessary and Sufficient for Signal
    Dimerization of LTβRbyLTα1β2 is necessary and sufficient for signal transduction Jawahar Sudhamsua,1, JianPing Yina,1, Eugene Y. Chiangb, Melissa A. Starovasnika, Jane L. Groganb,2, and Sarah G. Hymowitza,2 Departments of aStructural Biology and bImmunology, Genentech, Inc., South San Francisco, CA 94080 Edited by K. Christopher Garcia, Stanford University, Stanford, CA, and approved October 24, 2013 (received for review June 6, 2013) Homotrimeric TNF superfamily ligands signal by inducing trimers survival in a xenogeneic human T-cell–dependent mouse model of of their cognate receptors. As a biologically active heterotrimer, graft-versus-host disease (GVHD) (11). Lymphotoxin(LT)α1β2 is unique in the TNF superfamily. How the TNFRSF members are typically activated by TNFSF-induced three unique potential receptor-binding interfaces in LTα1β2 trig- trimerization or higher order oligomerization, resulting in initiation ger signaling via LTβ Receptor (LTβR) resulting in lymphoid organ- of intracellular signaling processes including the canonical and ogenesis and propagation of inflammatory signals is poorly noncanonical NF-κB pathways (2, 3). Ligand–receptor interactions α β understood. Here we show that LT 1 2 possesses two binding induce higher order assemblies formed between adaptor motifs in sites for LTβR with distinct affinities and that dimerization of LTβR the cytoplasmic regions of the receptors such as death domains or α β fi by LT 1 2 is necessary and suf cient for signal transduction. The TRAF-binding motifs and downstream signaling components such α β β crystal structure of a complex formed by LT 1 2,LT R, and the fab as Fas-associated protein with death domain (FADD), TNFR1- fragment of an antibody that blocks LTβR activation reveals the associated protein with death domain (TRADD), and TNFR-as- lower affinity receptor-binding site.
    [Show full text]
  • LIGHT Is Expressed in Foam Cells and Involved in Destabilization of Atherosclerotic Plaques Through Induction of Matrix Metalloproteinase-9 and IL-8
    LIGHT is Expressed in Foam Cells and Involved in Destabilization of Atherosclerotic Plaques through Induction of Matrix Metalloproteinase-9 and IL-8 Won-Jung Kim and Won-Ha Lee Department of Genetic Engineering, Kyungpook National University, Daegu, Korea ABSTRACT Background: LIGHT (TNFSF14) is a member of tumor necrosis factor superfamily and is the ligand for TR2 (TNFRSF14/HVEM). LIGHT is known to have pro- inflammatory roles in atherosclerosis. Methods: To find out the expression pattern of LIGHT in atherosclerotic plaques, immunohistochemical analysis was performed on human carotid atherosclerotic plaque specimens. LIGHT induced atherogenic events using human monocytic cell line THP-1 were also investigated. Results: Imm- unohistochemical analysis revealed expression of LIGHT and TR2 in foam cell rich regions in the atherosclerotic plaques. Double immunohistochemical analysis further confirmed the expression of LIGHT in foam cells. Stimulation of THP-1 cells, which express TR2, with either recombinant LIGHT or immobilized anti-TR2 monoclonal antibody induced interleukin-8 and matrix metalloproteinase(MMP)-9. Electrophoretic mobility shift assay demonstrated that LIGHT induces nuclear localization of tran- scription factor, nuclear factor (NF)-κB. LIGHT induced activation of MMP-9 is mediated by NF-κB, since treatment of THP-1 cells with the NF-κB inhibitor PDTC (pyrrolidine dithiocarbamate) completely blocked the activation of MMP-9. Conclusion: These data indicate that LIGHT is expressed in foam cells in atherosclerotic plaques and is involved in atherogenesis through activation of pro-atherogenic cytokine IL-8 and destabilization of plaque by inducing matrix degrading enzyme. (Immune Network 2004;4(2):116-122) Key Words: Atherosclerosis, inflammation, matrix metalloproteinase, LIGHT, TNFSF inflammatory cytokines and matrix metallopro- Introduction teinases, and expression of adhesion molecules and Members of tumor necrosis factor superfamily tissue factor (7,8).
    [Show full text]
  • Death of HT29 Adenocarcinoma Cells Induced by TNF Family Receptor Activation Is Caspase-Independent and Displays Features of Both Apoptosis and Necrosis
    Cell Death and Differentiation (2002) 9, 1321 ± 1333 ã 2002 Nature Publishing Group All rights reserved 1350-9047/02 $25.00 www.nature.com/cdd Death of HT29 adenocarcinoma cells induced by TNF family receptor activation is caspase-independent and displays features of both apoptosis and necrosis 1 ,1 CA Wilson and JL Browning* Introduction 1 Department of Exploratory Biology, Biogen, 12 Cambridge Center, Cambridge, Receptors in the TNF family can initiate both canonical MA 02142, USA apoptotic and necrotic death events.1 Prototypical apoptosis * Corresponding author: JL Browning, Department of Exploratory Biology, follows activation of the Fas receptor on T cells leading to Biogen, 12 Cambridge Center, Cambridge, MA 02142, USA; caspase activation and a cascade of events eventually Tel: 617 679-3312; Fax: 617 679-2304; E-mail: [email protected] culminating in the various hallmarks of apoptosis.2,3 Yet even Received 7.12.01; revised 26.1.02; accepted 22.7.02 in this familiar case, Fas/FADD can trigger necrosis in T cells 4,5 Edited by B Osborne in the absence of caspase signaling. In the well-studied L929 fibroblast line, Fas activation triggers apoptosis while TNF initiates a necrotic event that is actually enhanced by Abstract caspase inhibition.1 Similarly, TNF signaling in the presence of caspase inhibitors was reported to lead to the necrosis of The HT29 adenocarcinoma is a common model of epithelial NIH3T3 fibroblasts and the myeloid U937 cell line.6 It has cell differentiation and colorectal cancer and its death is an oft- been dogmatic that apoptosis is only initiated by those TNF analyzed response to TNF family receptor signaling.
    [Show full text]
  • The Unexpected Role of Lymphotoxin Β Receptor Signaling
    Oncogene (2010) 29, 5006–5018 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW The unexpected role of lymphotoxin b receptor signaling in carcinogenesis: from lymphoid tissue formation to liver and prostate cancer development MJ Wolf1, GM Seleznik1, N Zeller1,3 and M Heikenwalder1,2 1Department of Pathology, Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland and 2Institute of Virology, Technische Universita¨tMu¨nchen/Helmholtz Zentrum Mu¨nchen, Munich, Germany The cytokines lymphotoxin (LT) a, b and their receptor genesis. Consequently, the inflammatory microenviron- (LTbR) belong to the tumor necrosis factor (TNF) super- ment was added as the seventh hallmark of cancer family, whose founder—TNFa—was initially discovered (Hanahan and Weinberg, 2000; Colotta et al., 2009). due to its tumor necrotizing activity. LTbR signaling This was ultimately the result of more than 100 years of serves pleiotropic functions including the control of research—indeed—the first observation that tumors lymphoid organ development, support of efficient immune often arise at sites of inflammation was initially reported responses against pathogens due to maintenance of intact in the nineteenth century by Virchow (Balkwill and lymphoid structures, induction of tertiary lymphoid organs, Mantovani, 2001). Today, understanding the underlying liver regeneration or control of lipid homeostasis. Signal- mechanisms of why immune cells can be pro- or anti- ing through LTbR comprises the noncanonical/canonical carcinogenic in different types of tumors and which nuclear factor-jB (NF-jB) pathways thus inducing cellular and molecular inflammatory mediators (for chemokine, cytokine or adhesion molecule expression, cell example, macrophages, lymphocytes, chemokines or proliferation and cell survival.
    [Show full text]
  • Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma
    diagnostics Article Loss of Lymphotoxin Alpha-Expressing Memory B Cells Correlates with Metastasis of Human Primary Melanoma Franziska Werner 1 , Christine Wagner 1, Martin Simon 1, Katharina Glatz 2, Kirsten D. Mertz 3,4 , Heinz Läubli 5 , Erika Richtig 6, Johannes Griss 7 and Stephan N. Wagner 1,* 1 Laboratory of Molecular Dermato-Oncology and Tumor Immunology, Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria; [email protected] (F.W.); [email protected] (C.W.); [email protected] (M.S.) 2 Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland; [email protected] 3 Institute of Pathology, Cantonal Hospital Baselland, 4410 Liestal, Switzerland; [email protected] 4 University of Basel, 4001 Basel, Switzerland 5 Laboratory for Cancer Immunotherapy, Department of Biomedicine and Medical Oncology, Department of Internal Medicine, University Hospital Basel, 4031 Basel, Switzerland; [email protected] 6 Department of Dermatology, Medical University of Graz, 8036 Graz, Austria; [email protected] 7 Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria; [email protected] * Correspondence: [email protected] Abstract: Activated antigen-experienced B cells play an unexpected complex role in anti-tumor immunity in human melanoma patients. However, correlative studies between B cell infiltration and Citation: Werner, F.; Wagner, C.; tumor progression are limited by the lack of distinction between functional B cell subtypes. In this Simon, M.; Glatz, K.; Mertz, K.D.; study, we examined a series of 59 primary and metastatic human cutaneous melanoma specimens Läubli, H.; Richtig, E.; Griss, J.; with B cell infiltration.
    [Show full text]
  • Targeting the Lymphotoxin-B Receptor with Agonist Antibodies As a Potential Cancer Therapy
    Research Article Targeting the Lymphotoxin-B Receptor with Agonist Antibodies as a Potential Cancer Therapy Matvey Lukashev,1 Doreen LePage,1 Cheryl Wilson,1 Ve´ronique Bailly,1 Ellen Garber,1 AlexLukashin, 1 Apinya Ngam-ek,1 Weike Zeng,1 Norman Allaire,1 Steve Perrin,1 Xianghong Xu,1 Kendall Szeliga,1 Kathleen Wortham,1 Rebecca Kelly,1 Cindy Bottiglio,1 Jane Ding,1 Linda Griffith,1 Glenna Heaney,1 Erika Silverio,1 William Yang,1 Matt Jarpe,1 Stephen Fawell,1 Mitchell Reff,1 Amie Carmillo,1 Konrad Miatkowski,1 Joseph Amatucci,1 Thomas Crowell,1 Holly Prentice,1 Werner Meier, 1 Shelia M. Violette,1 Fabienne Mackay,1 Dajun Yang,2 Robert Hoffman,3 and Jeffrey L. Browning1 1Departments of Immunobiology, Oncopharmacology, Molecular Engineering, Molecular Profiling, Molecular Discovery, Antibody Humanization, and Cellular Engineering, Biogen Idec, Cambridge, Massachusetts; 2Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan; and 3AntiCancer, Inc., San Diego, California Abstract receptor (TRAILR) 1/2, death receptor (DR) 3, DR6, and possibly ectodermal dysplasia receptor (EDAR). These TNFRs harbor The lymphotoxin-B receptor (LTBR) is a tumor necrosis factor signaling adaptor motifs termed death domains that can initiate receptor family member critical for the development and the extrinsic apoptosis program. In addition, TNFRs of this group maintenance of various lymphoid microenvironments. Herein, can exert antitumor effects via other mechanisms that include we show that agonistic anti-LTBR monoclonal antibody (mAb) tumor sensitization to chemotherapeutic agents, activation of CBE11 inhibited tumor growth in xenograft models and antitumor immunity, and disruption of tumor-associated micro- potentiated tumor responses to chemotherapeutic agents.
    [Show full text]
  • Expression Il2 Differentiation by Promoting TNFR2 Impairs Th17
    Transmembrane TNF−TNFR2 Impairs Th17 Differentiation by Promoting Il2 Expression Patrick G. Miller, Michael B. Bonn and Susan C. McKarns This information is current as J Immunol 2015; 195:2633-2647; Prepublished online 12 of October 3, 2021. August 2015; doi: 10.4049/jimmunol.1500286 http://www.jimmunol.org/content/195/6/2633 Downloaded from References This article cites 76 articles, 37 of which you can access for free at: http://www.jimmunol.org/content/195/6/2633.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on October 3, 2021 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 © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Transmembrane TNF–TNFR2 Impairs Th17 Differentiation by Promoting Il2 Expression Patrick G. Miller,* Michael B. Bonn,* and Susan C. McKarns*,† The double-edged sword nature by which IL-2 regulates autoimmunity and the unpredictable outcomes of anti-TNF therapy in autoimmunity highlight the importance for understanding how TNF regulates IL-2.
    [Show full text]
  • Targeting and Utilizing Primary Tumors As Live Vaccines: Changing Strategies
    Cellular & Molecular Immunology (2012) 9, 20–26 ß 2012 CSI and USTC. All rights reserved 1672-7681/12 $32.00 www.nature.com/cmi REVIEW Targeting and utilizing primary tumors as live vaccines: changing strategies Xuanming Yang, Eric D Mortenson and Yang-Xin Fu Tumor metastases and relapse are the major causes of morbidity and mortality in cancer. Although surgery, chemotherapy and/or radiation therapy can typically control primary tumor growth, metastatic and relapsing tumors are often inaccessible or resistant to these treatments. An adaptive immune response can be generated during these conventional treatments of the primary tumor, and presumably both the primary tumor and secondary metastases share many of the same or similar antigenic characteristics recognized by the immune system. Thus, when established, this response should be able to control metastatic growth and tumor relapse. This review summarizes the mechanisms by which antitumor immune responses are generated, and recent findings supporting the hypothesis that many therapies targeting primary tumors can generate antitumor adaptive immune responses to prevent metastases and tumor relapse. Cellular & Molecular Immunology (2012) 9, 20–26; doi:10.1038/cmi.2011.49; published online 21 November 2011 Keywords: chemotherapy; immunotherapy; metastasis; radiotherapy; tumor vaccine INTRODUCTION tissues.3–5 Thus, overcoming tumor-associated immune-suppressive Conventional treatments such as surgery and chemotherapy are effec- mechanisms to induce potent antitumor immunity is the first step for tive means of eliminating or reducing primary tumor growth, but have effective cancer immunotherapy.5–7 Many mechanisms are involved not proved effective in eradicating metastases. Because metastatic dis- in tumor-associated immune suppression of naive and previously ease may not respond similarly to chemotherapies used in treating the activated T cells.
    [Show full text]
  • Rapid and Rigorous IL-17A Production by a Distinct
    Rapid and Rigorous IL-17A Production by a Distinct Subpopulation of Effector Memory T Lymphocytes Constitutes a Novel Mechanism of Toxic Shock Syndrome Immunopathology This information is current as of September 28, 2021. Peter A. Szabo, Ankur Goswami, Delfina M. Mazzuca, Kyoungok Kim, David B. O'Gorman, David A. Hess, Ian D. Welch, Howard A. Young, Bhagirath Singh, John K. McCormick and S. M. Mansour Haeryfar J Immunol published online 20 February 2017 Downloaded from http://www.jimmunol.org/content/early/2017/02/18/jimmun ol.1601366 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2017/02/18/jimmunol.160136 Material 6.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • 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 © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published February 20, 2017, doi:10.4049/jimmunol.1601366 The Journal of Immunology Rapid and Rigorous IL-17A Production by a Distinct Subpopulation of Effector Memory T Lymphocytes Constitutes a Novel Mechanism of Toxic Shock Syndrome Immunopathology Peter A.
    [Show full text]
  • Targeting Lymphotoxin Beta and Paired Box 5: a Potential
    Huang et al. Cancer Cell Int (2021) 21:3 https://doi.org/10.1186/s12935-020-01632-x Cancer Cell International PRIMARY RESEARCH Open Access Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis Runzhi Huang1,2†, Zhiwei Zeng1†, Penghui Yan1†, Huabin Yin3, Xiaolong Zhu1, Peng Hu1, Juanwei Zhuang1, Jiaju Li1, Siqi Li4, Dianwen Song3*, Tong Meng2,3* and Zongqiang Huang1*† Abstract Background: Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with diferentially expressed genes and tumor-infltrating cells. Methods: RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related diferentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most signifcant immune genes. CIBERSORT algorithm was performed to identify signifcant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis- related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were vali- dated by single-cell RNA sequencing and ChIP sequencing data. Results: A total of 204 immune genes and 12 TFs, were identifed. The prediction model achieved a satisfactory efec- tiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was signifcantly correlated with PAX5 (P < 0.001, R 0.829) and hematopoietic cell lineage pathway (P < 0.001, R 0.375).
    [Show full text]
  • The Expression of Genes Contributing to Pancreatic Adenocarcinoma Progression Is Influenced by the Respective Environment – Sagini Et Al
    The expression of genes contributing to pancreatic adenocarcinoma progression is influenced by the respective environment – Sagini et al Supplementary Figure 1: Target genes regulated by TGM2. Figure represents 24 genes regulated by TGM2, which were obtained from Ingenuity Pathway Analysis. As indicated, 9 genes (marked red) are down-regulated by TGM2. On the contrary, 15 genes (marked red) are up-regulated by TGM2. Supplementary Table 1: Functional annotations of genes from Suit2-007 cells growing in pancreatic environment Categoriesa Diseases or p-Valuec Predicted Activation Number of genesf Functions activationd Z-scoree Annotationb Cell movement Cell movement 1,56E-11 increased 2,199 LAMB3, CEACAM6, CCL20, AGR2, MUC1, CXCL1, LAMA3, LCN2, COL17A1, CXCL8, AIF1, MMP7, CEMIP, JUP, SOD2, S100A4, PDGFA, NDRG1, SGK1, IGFBP3, DDR1, IL1A, CDKN1A, NREP, SEMA3E SERPINA3, SDC4, ALPP, CX3CL1, NFKBIA, ANXA3, CDH1, CDCP1, CRYAB, TUBB2B, FOXQ1, SLPI, F3, GRINA, ITGA2, ARPIN/C15orf38- AP3S2, SPTLC1, IL10, TSC22D3, LAMC2, TCAF1, CDH3, MX1, LEP, ZC3H12A, PMP22, IL32, FAM83H, EFNA1, PATJ, CEBPB, SERPINA5, PTK6, EPHB6, JUND, TNFSF14, ERBB3, TNFRSF25, FCAR, CXCL16, HLA-A, CEACAM1, FAT1, AHR, CSF2RA, CLDN7, MAPK13, FERMT1, TCAF2, MST1R, CD99, PTP4A2, PHLDA1, DEFB1, RHOB, TNFSF15, CD44, CSF2, SERPINB5, TGM2, SRC, ITGA6, TNC, HNRNPA2B1, RHOD, SKI, KISS1, TACSTD2, GNAI2, CXCL2, NFKB2, TAGLN2, TNF, CD74, PTPRK, STAT3, ARHGAP21, VEGFA, MYH9, SAA1, F11R, PDCD4, IQGAP1, DCN, MAPK8IP3, STC1, ADAM15, LTBP2, HOOK1, CST3, EPHA1, TIMP2, LPAR2, CORO1A, CLDN3, MYO1C,
    [Show full text]