Deficiency in Interleukin-18 Ameliorated Glial Activation And
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Ccl9 Induced by Tgf-Β Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Lung
CCL9 INDUCED BY TGF-β SIGNALING IN MYELOID CELLS ENHANCES TUMOR CELL SURVIVAL IN THE PREMETASTATIC LUNG by Hangyi Yan A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland March, 2015 ABSTRACT The majority of cancer patients die from metastasis. To achieve metastasis, tumor cells must first survive and then proliferate to form colonies. Compelling data have shown the indispensable participation of host microenvironment for metastasis. Bone marrow derived myeloid cells sculpt a tumor-promoting microenvironment in the premetastatic organs prior to tumor cell arrival. However, the molecular mechanisms for this “seed and soil” hypothesis are unclear. Here we report that CCL9 was significantly produced and secreted by Gr-1+CD11b+ cells when co-cultured with tumor cells, and in the premetastatic lung. CCL9 knockdown (KD) in myeloid cells decreased metastasis, and this process signaled through its sole receptor CCR1. Overexpression of CCR1 lost the metastasis-promoting function in the context of CCL9 KD. CCL9 enhanced tumor cell survival in the premetastatic organs. The underlying molecular mechanisms included activation of cell survival factors phosphorylated AKT and BCL-2, as well as inhibition of Poly (ADP-ribose) polymerase (PARP)-dependent apoptosis pathway. Additionally, CCL9/CCR1 had autocrine effects, which enhanced CCL9 secretion and the survival of Gr-1+CD11b+ cells. We found that CCL9 was a key effector of myeloid transforming growth factor β (TGF-β) pathway that promotes metastasis. Decreased metastasis in mice with myeloid specific TGF-β receptor II deletion (Tgfbr2MyeKO) correlated with lower CCL9 expression in TGF-β deficient myeloid cells. -
Interleukin (IL)17A, F and AF in Inflammation: a Study in Collageninduced Arthritis and Rheumatoid Arthritis
bs_bs_banner Clinical and Experimental Immunology ORIGINAL ARTICLE doi:10.1111/cei.12376 Interleukin (IL)-17A, F and AF in inflammation: a study in collagen-induced arthritis and rheumatoid arthritis S. Sarkar,* S. Justa,* M. Brucks,* Summary J. Endres,† D. A. Fox,† X. Zhou,* Interleukin (IL)-17 plays a critical role in inflammation. Most studies to date F. Alnaimat,* B. Whitaker,‡ have elucidated the inflammatory role of IL-17A, often referred to as IL-17. J. C. Wheeler,‡ B. H. Jones§ and IL-17F is a member of the IL-17 family bearing 50% homology to IL-17A S. R. Bommireddy* and can also be present as heterodimer IL-17AF. This study elucidates the *Section of Rheumatology, Department of Medicine, and the Arizona Arthritis Center, distribution and contribution of IL-17A, F and AF in inflammatory arthritis. University of Arizona, Tucson, AZ, †Divison of Neutralizing antibody to IL-17A alone or IL-17F alone or in combination Rheumatology, Department of Internal Medicine, was utilized in the mouse collagen-induced arthritis (CIA) model to eluci- University of Michigan, Ann Arbor, MI, and date the contribution of each subtype in mediating inflammation. IL-17A, F ‡Biologics Research and §Immunology Discovery and AF were all increased during inflammatory arthritis. Neutralization of Research, Janssen Research and Development, IL-17A reduced the severity of arthritis, neutralization of IL-17A+IL-17F had Spring House, PA, USA the same effect as neutralizing IL-17A, while neutralization of IL-17F had no effect. Moreover, significantly higher levels of IL-17A and IL-17F were detected in peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA). -
Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes
Published OnlineFirst February 18, 2016; DOI: 10.1158/0008-5472.CAN-15-1548 Cancer Tumor and Stem Cell Biology Research Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor- Infiltrating Lymphocytes Geoffrey J. Markowitz1, Pengyuan Yang1,2,3, Jing Fu3, Gregory A. Michelotti4, Rui Chen1, Jianhua Sui5, Bin Yang2, Wen-Hao Qin3, Zheng Zhang6, Fu-Sheng Wang6, Anna Mae Diehl4, Qi-Jing Li7, Hongyang Wang3, and Xiao-Fan Wang1 Abstract Chronic inflammation in liver tissue is an underlying cause of IL18R1 deletion increased tumor burden. Mechanistically, we hepatocellular carcinoma. High levels of inflammatory cytokine foundthatIL18exertedinflammation-dependent tumor-sup- IL18 in the circulation of patients with hepatocellular carcinoma pressive effects largely by promoting the differentiation, activ- correlates with poor prognosis. However, conflicting results have ity, and survival of tumor-infiltrating T cells. Finally, differences been reported for IL18 in hepatocellular carcinoma development in the expression of IL18 in tumor tissue versus nontumor and progression. In this study, we used tissue specimens from tissueweremorepredictiveofpatientoutcomethanoverall hepatocellular carcinoma patients and clinically relevant mouse tissue expression. Taken together, our findings resolve a long- models of hepatocellular carcinoma to evaluate IL18 expression standing contradiction regarding a tumor-suppressive role for and function. In a mouse model of liver fibrosis that recapitulates IL18 in established hepatocellular carcinoma and provide a a tumor-promoting microenvironment, global deletion of the mechanistic explanation for the complex relationship between IL18 receptor IL18R1 enhanced tumor growth and burden. Sim- its expression pattern and hepatocellular carcinoma prognosis. ilarly, in a carcinogen-induced model of liver tumorigenesis, Cancer Res; 76(8); 1–12. -
Interleukin-33 Signaling Exacerbates Experimental Infectious Colitis by Enhancing Gut Permeability and Inhibiting Protective Th17 Immunity
www.nature.com/mi ARTICLE OPEN Interleukin-33 signaling exacerbates experimental infectious colitis by enhancing gut permeability and inhibiting protective Th17 immunity Vittoria Palmieri1, Jana-Fabienne Ebel1, Nhi Ngo Thi Phuong1, Robert Klopfleisch2, Vivian Pham Vu3,4, Alexandra Adamczyk1, Julia Zöller1, Christian Riedel5, Jan Buer1, Philippe Krebs3, Wiebke Hansen1, Eva Pastille1 and Astrid M. Westendorf 1 A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium.We observed that deficiency of the IL-33 signaling pathway attenuates bacterial-induced colitis. Conversely, boosting this pathway strongly aggravates the inflammatory response and makes the mice prone to systemic infection. Mechanistically, IL-33 mediates its detrimental effect by enhancing gut permeability and by limiting the induction of protective T helper 17 cells at the site of infection, thus impairing host defense mechanisms against the enteric pathogen. Importantly, IL-33-treated infected mice supplemented with IL-17A are able to resist the otherwise strong systemic spreading of the pathogen. These findings reveal a novel IL-33/IL-17A crosstalk that controls the pathogenesis of Citrobacter rodentium-driven infectious colitis. Manipulating the dynamics of cytokines may offer new therapeutic strategies to treat specific intestinal infections. 1234567890();,: Mucosal Immunology (2021) 14:923–936; https://doi.org/10.1038/s41385-021-00386-7 INTRODUCTION epithelial cells, and endothelial cells in response to injury6. -
The Importance of Microenvironment: the Role of CCL8 in Metastasis Formation of Melanoma
www.impactjournals.com/oncotarget/ Oncotarget, Vol. 6, No. 30 The importance of microenvironment: the role of CCL8 in metastasis formation of melanoma Tamás Barbai1, Zsuzsanna Fejős1, Laszlo G. Puskas2, József Tímár1,3 and Erzsébet Rásó1,3 1 2nd Department of Pathology, Semmelweis University, Budapest, Hungary 2 Avidin Ltd., Szeged, Hungary 3 MTA-SE Tumor Progression Research Group, Budapest, Hungary Correspondence to: Tamás Barbai, email: [email protected] Keywords: melanoma metastasis, microenvironment, CCL8, miR146a Received: February 19, 2015 Accepted: July 16, 2015 Published: July 31, 2015 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT We have attempted to characterize the changes occurring on the host side during the progression of human melanoma. To investigate the role of tumor microenvironment, we set up such an animal model, which was able to isolate the host related factors playing central role in metastasis formation. One of these ’factors’, CCL12, was consequently selected and its behavior was examined alongside its human homologue (CCL8). In our animal model, metastasis forming primary melanoma in the host exhibited increased level of CCL12 mRNA expression. In clinical samples, when examining the tumor and the host together, the cumulative (tumor and host) CCL8 expression was lower in the group in which human primary melanoma formed lung metastasis compared to non-metastatic primary tumors. We could not detect significant difference in CCL8 receptor (CCR1) expression between the two groups. Increased migration of the examined tumor cell lines was observed when CCL8 was applied as a chemoattractant. -
IL-17-Producing Cells in Tumor Immunity: Friends Or Foes?
Immune Netw. 2020 Feb;20(1):e6 https://doi.org/10.4110/in.2020.20.e6 pISSN 1598-2629·eISSN 2092-6685 Review Article IL-17-Producing Cells in Tumor Immunity: Friends or Foes? Da-Sol Kuen 1,2, Byung-Seok Kim 1, Yeonseok Chung 1,2,* 1Laboratory of Immune Regulation, Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea 2BK21 Plus Program, Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Korea Received: Dec 29, 2019 Revised: Jan 25, 2020 ABSTRACT Accepted: Jan 26, 2020 IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells *Correspondence to including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological Yeonseok Chung significance of IL-17-producing cells is well-studied in contexts of inflammation, Laboratory of Immune Regulation and BK21 Plus Program, Institute of Pharmaceutical autoimmunity and host defense against infection. While most of available studies in tumor + Sciences, Seoul National University, 1 Gwanak- immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8 ro, Gwanak-gu, Seoul 08826, Korea. T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains E-mail: [email protected] poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in Copyright © 2020. The Korean Association of adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic Immunologists potential of IL-17-producing cells. This review discusses the features of IL-17-producing This is an Open Access article distributed cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti- under the terms of the Creative Commons tumorigenic functions in an organ-dependent context. -
Evolutionary Divergence and Functions of the Human Interleukin (IL) Gene Family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W
UPDATE ON GENE COMPLETIONS AND ANNOTATIONS Evolutionary divergence and functions of the human interleukin (IL) gene family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W. Nebert3* and Vasilis Vasiliou1 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected]; [email protected] Date received (in revised form): 22nd September 2010 Abstract Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term ‘interleukin’ (IL) has been used to describe a group of cytokines with complex immunomodulatory functions — including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host’s immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type. -
Decrease in Mucosal IL17A, IFN and IL10 Expressions in Active Crohn's
nutrients Article Decrease in Mucosal IL17A, IFNγ and IL10 Expressions in Active Crohn’s Disease Patients Treated with High-Dose Vitamin D Alone or Combined with Infliximab Mia Bendix 1,*, Anders Dige 1, Søren Peter Jørgensen 1, Jens Frederik Dahlerup 1 , Bo Martin Bibby 2, Bent Deleuran 3,4 and Jørgen Agnholt 1 1 Department of Hepatology and Gastroenterology, Aarhus University Hospital, 8200 Aarhus, Denmark; [email protected] (A.D.); [email protected] (S.P.J.); [email protected] (J.F.D.); [email protected] (J.A.) 2 Department of Public Health—Department of Biostatistics, Aarhus University, 8000 Aarhus, Denmark; [email protected] 3 Department of Rheumatology, Aarhus University Hospital, 8200 Aarhus, Denmark; [email protected] 4 Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark * Correspondence: [email protected] Received: 5 November 2020; Accepted: 26 November 2020; Published: 30 November 2020 Abstract: Background: Vitamin D treatment may reduce Crohn’s disease (CD) activity by modulating the mucosal immune function. We investigated if high-dose vitamin D +/ infliximab modulated − the mucosal cytokine expression in active CD. Methods: Forty CD patients were randomized into: infliximab + vitamin D; infliximab + placebo-vitamin D; placebo-infliximab + vitamin D or placebo-infliximab + placebo-vitamin D. Infliximab (5 mg/kg) and placebo-infliximab were administered at weeks 0, 2 and 6. Oral vitamin D was administered as bolus 200,000 international units (IU) per week 0 followed by 20,000 IU/day for 7 weeks or placebo. Endoscopy with biopsies was performed at weeks 0 and 7 where endoscopic activity was measured and mucosal mRNA cytokine expression was examined. -
Il1f10 (NM 153077) Mouse Tagged ORF Clone – MR223925 | Origene
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for MR223925 Il1f10 (NM_153077) Mouse Tagged ORF Clone Product data: Product Type: Expression Plasmids Product Name: Il1f10 (NM_153077) Mouse Tagged ORF Clone Tag: Myc-DDK Symbol: Il1f10 Synonyms: MGC130267; MGC130268 Vector: pCMV6-Entry (PS100001) E. coli Selection: Kanamycin (25 ug/mL) Cell Selection: Neomycin ORF Nucleotide >MR223925 ORF sequence Sequence: Red=Cloning site Blue=ORF Green=Tags(s) TTTTGTAATACGACTCACTATAGGGCGGCCGGGAATTCGTCGACTGGATCCGGTACCGAGGAGATCTGCC GCCGCGATCGCC ATGTGCTCCCTTCCCATGGCAAGATACTACATAATCAAGGATGCACATCAAAAGGCTTTGTACACACGGA ATGGCCAGCTCCTGCTGGGAGACCCTGATTCAGACAATTATAGTCCAGAGAAGGTCTGTATCCTTCCTAA CCGAGGCCTAGACCGCTCCAAGGTCCCCATCTTCCTGGGGATGCAGGGAGGAAGTTGCTGCCTGGCGTGT GTAAAGACAAGAGAGGGACCTCTCCTGCAGCTGGAGGATGTGAACATCGAGGACCTATACAAGGGAGGTG AACAAACCACCCGTTTCACCTTTTTCCAGAGAAGCTTGGGATCTGCCTTCAGGCTTGAGGCTGCTGCCTG CCCTGGCTGGTTTCTCTGTGGCCCAGCTGAGCCCCAGCAGCCAGTGCAGCTCACCAAAGAGAGTGAACCC TCCACCCATACTGAATTCTACTTTGAGATGAGTCGG ACGCGTACGCGGCCGCTCGAGCAGAAACTCATCTCAGAAGAGGATCTGGCAGCAAATGATATCCTGGATT ACAAGGATGACGACGATAAGGTTTAA Protein Sequence: >MR223925 protein sequence Red=Cloning site Green=Tags(s) MCSLPMARYYIIKDAHQKALYTRNGQLLLGDPDSDNYSPEKVCILPNRGLDRSKVPIFLGMQGGSCCLAC VKTREGPLLQLEDVNIEDLYKGGEQTTRFTFFQRSLGSAFRLEAAACPGWFLCGPAEPQQPVQLTKESEP STHTEFYFEMSR TRTRPLEQKLISEEDLAANDILDYKDDDDKV Restriction Sites: SgfI-MluI This product is to -
IL1F10 Monoclonal Antibody
Product Datasheet IL1F10 Monoclonal Antibody Catalog No: #42049 Orders: [email protected] Description Support: [email protected] Product Name IL1F10 Monoclonal Antibody Host Species Mouse Clonality Monoclonal Purification protein G purifed Applications IHC Species Reactivity Hu Specificity specific for Human IL1F10 denatured and native forms Immunogen Type protein Immunogen Description Recombinant Human IL1F10 protein Target Name IL1F10 Other Names IL-1F10, Family of interleukin 1-theta, FIL1 theta Interleukin-1 HY2, IL-1HY2, Interleukin-1 theta, IL-1 theta Interleukin-38, IL-38 Accession No. Swiss-Prot#: Q8WWZ1 Concentration 1.0mg/mL Formulation Preservative: 0.03% Proclin 300 Constituents: 50% Glycerol, 0.01M PBS, PH 7.4 Storage Store at -20°C Application Details Immunohistochemistry: 1:20 - 1:200 Images Immunohistochemical analysis of paraffin-embedded Human Colon cancer tissue using #42049 at dilution of 1:200. Address: 8400 Baltimore Ave. Suite 302 College Park MD 20740 USA http://www.sabbiotech.com 1 Immunohistochemical analysis of paraffin-embedded Human live cancer tissue using #42049 at dilution of 1:200. Immunohistochemical analysis of paraffin-embedded Human spleen tissue using #42049 at dilution of 1:200. Background Cytokine with immunomodulatory activity. Alone, does not induce cytokine production, but reduces IL22 and IL17A production by T-cells in response to heat-killed Candida albicans. Reduces IL36G-induced production of IL8 by peripheral blood mononuclear cells. Increases IL6 production by dendritic cells stimulated by bacterial lipopolysaccharides (LPS). Ligand for IL-36R/IL1RL2. References "IL-38 binds to the IL-36 receptor and has biological effects on immune cells similar to IL-36 receptor antagonist." van de Veerdonk F.L., Stoeckman A.K., Wu G., Boeckermann A.N., Azam T., Netea M.G., Joosten L.A., van der Meer J.W., Hao R., Kalabokis V., Dinarello C.A. -
Mixed Lineage Kinase 3 Inhibition Induces T Cell Activation and Cytotoxicity
Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity Sandeep Kumara, Sunil Kumar Singha, Navin Viswakarmaa, Gautam Sondarvaa, Rakesh Sathish Naira, Periannan Sethupathia, Subhash C. Sinhab, Rajyasree Emmadic, Kent Hoskinsd, Oana Danciud, Gregory R. J. Thatchere, Basabi Ranaa,f,g, and Ajay Ranaa,f,g,1 aDepartment of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612; bLaboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065; cDepartment of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612; dDivision of Hematology/Oncology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612; eDepartment of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612; fUniversity of Illinois Hospital and Health Sciences System Cancer Center, University of Illinois at Chicago, Chicago, IL 60612; and gResearch Unit, Jesse Brown VA Medical Center, Chicago, IL 60612 Edited by Michael Karin, University of California San Diego School of Medicine, La Jolla, CA, and approved February 26, 2020 (received for review December 5, 2019) Mixed lineage kinase 3 (MLK3), also known as MAP3K11, was cytotoxic effects of chemotherapeutic agents in estrogen receptor- + initially identified in a megakaryocytic cell line and is an emerging positive (ER ) breast cancer (3). We also reported that MLK3 is therapeutic target in cancer, yet its role in immune cells is not inhibited by human epidermal growth factor receptor 2 (HER2) known. Here, we report that loss or pharmacological inhibition amplification, and this allows HER2+ breast cancer cells to pro- of MLK3 promotes activation and cytotoxicity of T cells. -
Chemokine Receptors and Chemokine Production by CD34+ Stem Cell-Derived Monocytes in Response to Cancer Cells
ANTICANCER RESEARCH 32: 4749-4754 (2012) Chemokine Receptors and Chemokine Production by CD34+ Stem Cell-derived Monocytes in Response to Cancer Cells MALGORZATA STEC, JAROSLAW BARAN, MONIKA BAJ-KRZYWORZEKA, KAZIMIERZ WEGLARCZYK, JOLANTA GOZDZIK, MACIEJ SIEDLAR and MAREK ZEMBALA Department of Clinical Immunology and Transplantation, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Cracow, Poland Abstract. Background: The chemokine-chemokine receptor The chemokine–chemokine receptor (CR) network is involved (CR) network is involved in the regulation of cellular in the regulation of leukocyte infiltration of tumours. infiltration of tumours. Cancer cells and infiltrating Leukocytes, including monocytes, migrate to the tumour via macrophages produce a whole range of chemokines. This the gradient of chemokines that are produced by tumour and study explored the expression of some CR and chemokine stromal cells, including monocyte-derived macrophages (1-4). production by cord blood stem cell-derived CD34+ Several chemokines are found in the tumour microenvironment monocytes and their novel CD14++CD16+ and and are involved in the regulation of tumour-infiltrating CD14+CD16– subsets in response to tumour cells. Material macrophages (TIMs), by controlling their directed migration to and Methods: CR expression was determined by flow the tumour and inhibiting their egress by regulation of cytometry and their functional activity by migration to angiogenesis and immune response to tumour cells and by chemoattractants.