DOCSLIB.ORG

Interleukin-20 Induced Cell Death in Renal Epithelial Cells and Was Associated with Acute Renal Failure

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Interleukin-20 Induced Cell Death in Renal Epithelial Cells and Was Associated with Acute Renal Failure Genes and Immunity (2008) 9, 395–404 & 2008 Macmillan Publishers Limited All rights reserved 1466-4879/08 $30.00 www.nature.com/gene ORIGINAL ARTICLE Interleukin-20 induced cell death in renal epithelial cells and was associated with acute renal failure H-H Li1,2, Y-H Hsu3, C-C Wei1,4, P-T Lee5,6, W-C Chen7 and M-S Chang1,2,3,8 1Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 3Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Medical Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan; 5Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6Division of Nephrology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung & National Yang-Ming University, School of Medicine, Taipei, Taiwan; 7Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan and 8Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan Acute renal failure is an abrupt decrease in renal function. Interleukin (IL)-10 inhibits ischemic and cisplatin-induced acute renal failure. We aimed to determine whether IL-20 affects renal tubular epithelial cells and is associated with acute renal failure. We analyzed the expression of IL-20 and its receptor (R) in the kidneys of rats with HgCl2-induced acute renal failure. Reverse transcription-PCR showed upregulated IL-20, and its receptors and immunohistochemical staining showed strongly expressed IL-20 protein in proximal tubular epithelial cells. We analyzed human proximal tubular epithelial (HK-2) cells, which expressed both IL-20 and its receptors. IL-20 specifically induced mitochondria-dependent apoptosis by activating caspase 9 in HK-2 cells. IL-20 also activated c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2, the downstream signals implicated in the apoptosis of HK-2 cells. Furthermore, IL-20 upregulated the transcripts of transforming growth factor (TGF)-b1, a critical mediator of renal injury. In hypoxic HK-2 cells, IL-20 and IL-22R1 transcripts increased, and IL-20 upregulated IL-1b transcripts. In vivo study further demonstrated that anti-IL-20 antibody reduced the expression of TGF-b1 and IL-1b and the number of damaged tubular cells in the kidneys of rats with acute renal failure. We concluded that IL-20 may be involved in the injury of renal epithelial cells in acute renal failure. Genes and Immunity (2008) 9, 395–404; doi:10.1038/gene.2008.28; published online 22 May 2008 Keywords: IL-20; renal epithelial cell; apoptosis; necrosis Introduction Acute renal failure is a rapid drop in the glomerular filtration rate that leads to the accumulation of nitrogen- Interleukin (IL)-20 belongs to the IL-10 family, which ous waste such as serum creatinine and blood urea includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26.1 IL-20 nitrogen (BUN). There are many causes of acute renal is preferentially expressed in five major cell types: failure, but the most common is injury of renal tubular epithelial cells, myoepithelial cells, endothelial cells, epithelial cells by ischemia or cytotoxic regents,8 which macrophages and skeletal muscle cells.2 IL-20 induced resulted in their necrosis or apoptosis.9 There are two signal transducer and activator of transcription 3 activa- major apoptotic pathways in human ischemic acute renal tion. IL-20 directly activated signal transducer and failure. The intrinsic pathway requires translocation of activator of transcription 3 either through IL-20 receptor Bax to the mitochondria followed by the release of (R) complex IL-20R1/IL-20R2 or through IL-20 receptor cytochrome c and activation of caspase 9. The extrinsic complex IL-22R1/IL-20R2.3 IL-20 has potent inflamma- pathway is through the activation of caspase 8.10 4,5 6 tory, angiogenic and chemoattractive characteristics. Although animals with HgCl2-induced nephrotoxicity IL-20 targeted keratinocytes, endothelial cells and syno- provide a well-established animal model for studying vial fibroblasts and was associated with psoriasis,7 acute renal failure, we do not have a detailed under- rheumatoid arthritis6 and atherosclerosis.5 standing of the toxicological mechanism of this model. One possibility is lipid peroxidation associated with the development of mild necrosis in proximal tubule Correspondence: Professor M-S Chang, Department of Biochemi- epithelial cells.11 Another possibility is mercury-induced stry and Molecular Biology, National Cheng Kung University, ion imbalances leading to renal toxicity.12 Moreover, College of Medicine, Tainan 70428, Taiwan. nephrotoxin-reduced renal blood flow resulted in renal E-mail: [email protected] ischemia.13 This work was supported by a grant from Chi Mei Medical Center, Tainan, Taiwan. Interleukin-10 is a pleiotropic cytokine with many Received 24 October 2007; revised 24 January 2008; accepted 20 immunosuppressive effects and a few immunostimula- March 2008; published online 22 May 2008 tory effects.14 Previous studies found that IL-10 IL-20-induced epithelial cell apoptosis H-H Li et al 396 decreased renal injury in animal models treated with and 2 (Figure 2B). We also investigated what kinds of either cisplatin or ischemia.15 IL-10 dramatically inhib- cells expressed rIL-20 in the kidneys of experimental rats. ited both inflammatory, cytotoxic and apoptotic path- rIL-20 was expressed in Henle’s loop and distal tubular ways of renal injury. As IL-20 is a member of the IL-10 epithelial cells in pretreated control rats (Figure 2Ca). family, we investigated whether IL-20 was also involved Two days after experimental rats had been injected with in the pathogenesis of acute renal failure. HgCl2, rIL-20 was strongly expressed in Henle’s loop, distal and proximal tubular epithelial cells (Figure 2Cc), Results Generating HgCl2-induced acute renal failure in rats To confirm that the rats in our animal model had HgCl2- induced acute renal failure, we analyzed their renal function. We collected their sera from day 0 to day 8. Serum creatinine levels began to rise on day 1, peaked on day 2 and returned to baseline on day 8 (Figure 1a). BUN levels began to rise on day 1, peaked on day 4 and returned to baseline on day 8 (Figure 1b). Transcripts of rat (r)IL-20 and its receptors increased in the kidneys of rats with HgCl2-induced acute renal failure To investigate whether IL-20 is involved in acute renal failure, we sacrificed the rats at different time points and compared the transcripts of rIL-20 and its receptors with those of healthy controls. Reverse transcription-PCR (RT- PCR) revealed that rIL-20, rIL-20R1, rIL-20R2 and rIL- 22R1 had increased in the kidneys of the experimental rats (those with acute renal failure) and had peaked on days 1 and 2 (Figure 2A). Protein expression of rIL-20 in the kidneys of experimental rats To confirm that the rIL-20 protein level as well as the transcript level had increased, we analyzed the kidney tissue using immunohistochemical staining with anti-IL- 20 antibodies. The expression levels of rIL-20 protein were upregulated and were strongly stained on days 1 Figure 2 Transcript levels and immunohistochemical staining of IL-20 and its receptors in the kidneys of rats with HgCl2-induced acute renal failure. Experimental rats were sacrificed at different times as indicated (day (D) 1 to D8) after they had been injected with HgCl2 on D0. (A) Total RNA was isolated from their kidneys for RT-PCR analysis with equal amounts of cDNA and primers specific for rat (r)IL-20, (r)IL-20R1, (r)IL-20R2 and (r)IL-22R1 to amplify the transcripts. b-actin was an internal control. Ctrl, control; H12, 12 h after injection of HgCl2.(B) Paraffined sections of kidney tissue were stained using anti-IL-20 monoclonal antibody 7E. The reaction was detected using 3-amino-9-ethylcarbazole chromogen stain (red), and the nuclei were counterstained with hematoxylin (blue) (magnification: Â 400). Experimental rats were killed at different times (as indicated) after they had been injected with HgCl2 on day 0. (C) The rats were killed on (a, b) day 0 and (c, d) Figure 1 Renal function in rats with HgCl2-induced acute renal day 2. In (a) and (c): P, proximal tubular epithelial cells; D, distal failure. (a) Serum creatinine and (b) BUN levels were detected at tubular epithelial cells; H, Henle’s loop. In (b) and (d): (n), different times (as indicated) after they had been injected with infiltrated immune cells; (k), urothelium in the renal pelvis; (m), HgCl2 on day 0. Values are means±s.e. (n ¼ 3/group). *Po0.05 smooth muscle cells. The figures represent similar patterns in three compared with controls (day 0). individual specimens. Genes and Immunity IL-20-induced epithelial cell apoptosis H-H Li et al 397 Figure 3 HK-2 cells expressed the transcripts and proteins of IL-20, IL-20R1, IL-20R2 and IL-22R1. (a) Total RNA was isolated for RT-PCR analysis with primers specific for human (h)IL-20, (h)IL-20R1, (h)IL-20R2 and (h)IL-22R1 to amplify the transcripts. NTC was a non-template control. (b) HK-2 cells were immunocytochemically stained using different monoclonal antibodies (as indicated). Mouse (m)IgG1 was a negative control. The reaction was detected using 3-amino-9-ethylcarbazole chromogen stain (red), and the nuclei were counterstained with hematoxylin (blue). infiltrated immune cells, urothelium in the renal pelvis, immunofluorescence images showed apoptotic cells and smooth muscle cells (Figure 2Cd). (green) (Figure 5c). There are two major apoptotic pathways in human IL-20 and its receptors were expressed in human proximal ischemic acute renal failure; the intrinsic and extrinsic tubular epithelial cells pathways.
Load more

Recommended publications
  • IL-1Β Induces the Rapid Secretion of the Antimicrobial Protein IL-26 From
    Published June 24, 2019, doi:10.4049/jimmunol.1900318 The Journal of Immunology IL-1b Induces the Rapid Secretion of the Antimicrobial Protein IL-26 from Th17 Cells David I. Weiss,*,† Feiyang Ma,†,‡ Alexander A. Merleev,x Emanual Maverakis,x Michel Gilliet,{ Samuel J. Balin,* Bryan D. Bryson,‖ Maria Teresa Ochoa,# Matteo Pellegrini,*,‡ Barry R. Bloom,** and Robert L. Modlin*,†† Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1b dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-g and IL-17A. IL-1b was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1b, inducing an NF-kB–regulated transcriptome. Finally, supernatants from IL-1b–treated memory T cells killed Escherichia coli in an IL-26–dependent manner. These results identify a mechanism by which human IL-1RI+ “antimicrobial Th17 cells” can be rapidly activated by IL-1b as part of the innate immune response to produce IL-26 to kill extracellular bacteria. The Journal of Immunology, 2019, 203: 000–000. cells are crucial for effective host defense against a wide and neutrophils.
    [Show full text]
  • 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.
    [Show full text]
  • Interleukin-19 Alleviates Experimental Autoimmune Encephalomyelitis by Attenuating Antigen-Presenting Cell Activation
    bioRxiv preprint doi: https://doi.org/10.1101/2020.07.15.204826; this version posted July 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Interleukin-19 alleviates experimental autoimmune encephalomyelitis 2 by attenuating antigen-presenting cell activation 3 4 Hiroshi Horiuchi1† , Bijay Parajuli1†, Hiroyasu Komiya2†, Yuki Ogawa2, Jin Shijie1, 5 Keita Takahashi2, Yasu-Taka Azuma3, Fumiaki Tanaka2, Akio Suzumura1, 6 and Hideyuki Takeuchi1, 2* 7 8 1Department of Neuroimmunology, Research Institute of Environmental Medicine, 9 Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601, Japan. 10 2Department of Neurology and Stroke Medicine, Yokohama City University Graduate 11 School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. 12 3Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka 13 Prefecture University Graduate School of Life and Environmental Science, Izumisano, 14 Osaka 598-8531, Japan. 15 16 †These authors contributed equally to this work. 17 18 *Corresponding Author: Hideyuki Takeuchi, M.D., Ph.D., Department of Neurology and 19 Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, 20 Kanazawa-ku, Yokohama 236-0004, Japan. 21 Phone: +81-45-787-2725, FAX: +81-45-788-6041, E-mail: [email protected] 22 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.15.204826; this version posted July 17, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.
    [Show full text]
  • Human Cytokine Response Profiles
    Comprehensive Understanding of the Human Cytokine Response Profiles A. Background The current project aims to collect datasets profiling gene expression patterns of human cytokine treatment response from the NCBI GEO and EBI ArrayExpress databases. The Framework for Data Curation already hosted a list of candidate datasets. You will read the study design and sample annotations to select the relevant datasets and label the sample conditions to enable automatic analysis. If you want to build a new data collection project for your topic of interest instead of working on our existing cytokine project, please read section D. We will explain the cytokine project’s configurations to give you an example on creating your curation task. A.1. Cytokine Cytokines are a broad category of small proteins mediating cell signaling. Many cell types can release cytokines and receive cytokines from other producers through receptors on the cell surface. Despite some overlap in the literature terminology, we exclude chemokines, hormones, or growth factors, which are also essential cell signaling molecules. Meanwhile, we count two cytokines in the same family as the same if they share the same receptors. In this project, we will focus on the following families and use the member symbols as standard names (Table 1). Family Members (use these symbols as standard cytokine names) Colony-stimulating factor GCSF, GMCSF, MCSF Interferon IFNA, IFNB, IFNG Interleukin IL1, IL1RA, IL2, IL3, IL4, IL5, IL6, IL7, IL9, IL10, IL11, IL12, IL13, IL15, IL16, IL17, IL18, IL19, IL20, IL21, IL22, IL23, IL24, IL25, IL26, IL27, IL28, IL29, IL30, IL31, IL32, IL33, IL34, IL35, IL36, IL36RA, IL37, TSLP, LIF, OSM Tumor necrosis factor TNFA, LTA, LTB, CD40L, FASL, CD27L, CD30L, 41BBL, TRAIL, OPGL, APRIL, LIGHT, TWEAK, BAFF Unassigned TGFB, MIF Table 1.
    [Show full text]
  • Targeting IL-10 Family Cytokines for the Treatment of Human Diseases
    Downloaded from http://cshperspectives.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Targeting IL-10 Family Cytokines for the Treatment of Human Diseases Xiaoting Wang,1 Kit Wong,2 Wenjun Ouyang,3 and Sascha Rutz4 1Department of Comparative Biology and Safety Sciences, Amgen, South San Francisco, California 94080 2Department of Biomarker Development, Genentech, South San Francisco, California 94080 3Department of Inflammation and Oncology, Amgen, South San Francisco, California 94080 4Department of Cancer Immunology, Genentech, South San Francisco, California 94080 Correspondence: [email protected]; [email protected] Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses during host defense but also in autoimmune disorders, inflammatory diseases, and cancer. Although IL-10 itself primarily acts on leukocytes and has potent immunosuppressive functions, other family members preferentially target nonimmune com- partments, such as tissue epithelial cells, where they elicit innate defense mechanisms to control viral, bacterial, and fungal infections, protect tissue integrity, and promote tissue repair and regeneration. As cytokines are prime drug targets, IL-10 family cytokines provide great opportunities for the treatment of autoimmune diseases, tissue damage, and cancer. Yet no therapy in this space has been approved to date. Here, we summarize the diverse biology of the IL-10 family as it relates to human disease and review past and current strategies and challenges to target IL-10 family cytokines for clinical use. nterleukin (IL)-10, a cytokine with pleiotropic kines (Fiorentino et al. 1989). It has since been Iimmunosuppressive functions, is also the found that IL-10 is expressed by a wide variety of founding member of the IL-10 family of cyto- cell types of both the innate and the adaptive kines (Fig.
    [Show full text]
  • Title Epithelial TRAF6 Drives IL-17-Mediated Psoriatic
    Epithelial TRAF6 drives IL-17-mediated psoriatic Title inflammation( Dissertation_全文 ) Author(s) Matsumoto, Reiko Citation 京都大学 Issue Date 2019-03-25 URL https://doi.org/10.14989/doctor.k21634 Right Type Thesis or Dissertation Textversion ETD Kyoto University RESEARCH ARTICLE Epithelial TRAF6 drives IL-17–mediated psoriatic inflammation Reiko Matsumoto,1 Teruki Dainichi,1 Soken Tsuchiya,2 Takashi Nomura,1 Akihiko Kitoh,1 Matthew S. Hayden,3 Ken J. Ishii,4,5 Mayuri Tanaka,4,5 Tetsuya Honda,1 Gyohei Egawa,1 Atsushi Otsuka,1 Saeko Nakajima,1 Kenji Sakurai,1 Yuri Nakano,1 Takashi Kobayashi,6 Yukihiko Sugimoto,2 and Kenji Kabashima1,7 1Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 2Department of Pharmaceutical Biochemistry, Kumamoto University Faculty of Life Sciences, Kumamoto, Japan. 3Section of Dermatology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. 4Laboratory of Adjuvant Innovation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan. 5Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan. 6Department of Infectious Disease Control, Faculty of Medicine, Oita University, Oita, Japan. 7Singapore Immunology Network (SIgN) and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore. Epithelial cells are the first line of defense against external dangers, and contribute to induction of adaptive immunity including Th17 responses. However, it is unclear whether specific epithelial signaling pathways are essential for the development of robust IL-17–mediated immune responses. In mice, the development of psoriatic inflammation induced by imiquimod required keratinocyte TRAF6. Conditional deletion of TRAF6 in keratinocytes abrogated dendritic cell activation, IL-23 production, and IL-17 production by γδ T cells at the imiquimod-treated sites.
    [Show full text]
  • Uniprot Nr. Proseek Panel 2,4-Dienoyl-Coa Reductase, Mitochondrial
    Protein Name (Short Name) Uniprot Nr. Proseek Panel 2,4-dienoyl-CoA reductase, mitochondrial (DECR1) Q16698 CVD II 5'-nucleotidase (5'-NT) P21589 ONC II A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAM-TS13) Q76LX8 CVD II A disintegrin and metalloproteinase with thrombospondin motifs 15 (ADAM-TS 15) Q8TE58 ONC II Adenosine Deaminase (ADA) P00813 INF I ADM (ADM) P35318 CVD II ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38) P28907 NEU I Agouti-related protein (AGRP) O00253 CVD II Alpha-2-macroglobulin receptor-associated protein (Alpha-2-MRAP) P30533 NEU I Alpha-L-iduronidase (IDUA) P35475 CVD II Alpha-taxilin (TXLNA) P40222 ONC II Aminopeptidase N (AP-N) P15144 CVD III Amphiregulin (AR) P15514 ONC II Angiopoietin-1 (ANG-1) Q15389 CVD II Angiopoietin-1 receptor (TIE2) Q02763 CVD II Angiotensin-converting enzyme 2 (ACE2) Q9BYF1 CVD II Annexin A1 (ANXA1) P04083 ONC II Artemin (ARTN) Q5T4W7 INF I Axin-1 (AXIN1) O15169 INF I Azurocidin (AZU1 P20160 CVD III BDNF/NT-3 growth factors receptor (NTRK2) Q16620 NEU I Beta-nerve growth factor (Beta-NGF) P01138 NEU I, INF I Bleomycin hydrolase (BLM hydrolase) Q13867 CVD III Bone morphogenetic protein 4 (BMP-4) P12644 NEU I Bone morphogenetic protein 6 (BMP-6) P22004 CVD II Brain-derived neurotrophic factor (BDNF) P23560 NEU I, INF I Brevican core protein (BCAN) Q96GW7 NEU I Brorin (VWC2) Q2TAL6 NEU I Brother of CDO (Protein BOC) Q9BWV1 CVD II Cadherin-3 (CDH3) P22223 NEU I Cadherin-5 (CDH5) P33151 CVD III Cadherin-6 (CDH6) P55285 NEU I Carbonic anhydrase 5A, mitochondrial
    [Show full text]
  • Supplemental Table S10. Differentially Expressed Interleukins Comparing SARS-Cov-2 Versus Medium
    Supplemental Table S10. Differentially expressed interleukins comparing SARS-CoV-2 versus medium ProbeName p ([SARS-CoV-2]Regulation Vs [Medium])FC ([SARS-CoV-2] ([SARS-CoV-2]GeneSymbol Vs Vs [Medium]) [Medium])Description A_33_P3211608 3,97E-02 up 2,974933 IL1RL1 Homo sapiens interleukin 1 receptor-like 1 (IL1RL1), transcript variant 4, non-coding RNA [NR_104167] A_23_P17053 6,39262E-05 up 6,132556 IL36G Homo sapiens interleukin 36, gamma (IL36G), transcript variant 1, mRNA [NM_019618] A_33_P3339625 1,17303E-05 up 16,473091 IL17C Homo sapiens interleukin 17C (IL17C), mRNA [NM_013278] A_33_P3243230 1,76904E-07 up 16,647413 HSINTLK8M interleukin 8 {Homo sapiens} (exp=-1; wgp=0; cg=0), partial (97%) [THC2544321] A_32_P223777 0,00139653 up 1,9878159 IL6ST Homo sapiens interleukin 6 signal transducer (IL6ST), transcript variant 1, mRNA [NM_002184] A_23_P76078 0,045698304 up 1,8592229 IL23A Homo sapiens interleukin 23, alpha subunit p19 (IL23A), mRNA [NM_016584] A_23_P336554 0,00221631 up 1,7976834 IL1RAP Homo sapiens interleukin 1 receptor accessory protein (IL1RAP), transcript variant 2, mRNA [NM_134470] A_33_P3251876 0,03411692 up 1,5917065 IL18R1 Homo sapiens interleukin 18 receptor 1 (IL18R1), transcript variant 1, mRNA [NM_003855] A_33_P3211666 0,026903022 up 1,5705488 IL18R1 Homo sapiens interleukin 18 receptor 1 (IL18R1), transcript variant 1, mRNA [NM_003855] A_23_P90925 0,004416244 up 2,695789 IL36B Homo sapiens interleukin 36, beta (IL36B), transcript variant 2, mRNA [NM_173178] A_24_P68783 0,000239245 up 2,834167 IL36RN Homo sapiens
    [Show full text]
  • A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression
    Supplementary Materials A Meta-Analysis of the Effects of High-LET Ionizing Radiations in Human Gene Expression Table S1. Statistically significant DEGs (Adj. p-value < 0.01) derived from meta-analysis for samples irradiated with high doses of HZE particles, collected 6-24 h post-IR not common with any other meta- analysis group. This meta-analysis group consists of 3 DEG lists obtained from DGEA, using a total of 11 control and 11 irradiated samples [Data Series: E-MTAB-5761 and E-MTAB-5754]. Ensembl ID Gene Symbol Gene Description Up-Regulated Genes ↑ (2425) ENSG00000000938 FGR FGR proto-oncogene, Src family tyrosine kinase ENSG00000001036 FUCA2 alpha-L-fucosidase 2 ENSG00000001084 GCLC glutamate-cysteine ligase catalytic subunit ENSG00000001631 KRIT1 KRIT1 ankyrin repeat containing ENSG00000002079 MYH16 myosin heavy chain 16 pseudogene ENSG00000002587 HS3ST1 heparan sulfate-glucosamine 3-sulfotransferase 1 ENSG00000003056 M6PR mannose-6-phosphate receptor, cation dependent ENSG00000004059 ARF5 ADP ribosylation factor 5 ENSG00000004777 ARHGAP33 Rho GTPase activating protein 33 ENSG00000004799 PDK4 pyruvate dehydrogenase kinase 4 ENSG00000004848 ARX aristaless related homeobox ENSG00000005022 SLC25A5 solute carrier family 25 member 5 ENSG00000005108 THSD7A thrombospondin type 1 domain containing 7A ENSG00000005194 CIAPIN1 cytokine induced apoptosis inhibitor 1 ENSG00000005381 MPO myeloperoxidase ENSG00000005486 RHBDD2 rhomboid domain containing 2 ENSG00000005884 ITGA3 integrin subunit alpha 3 ENSG00000006016 CRLF1 cytokine receptor like
    [Show full text]
  • And Neutralizes Its Activity IL-22 of a Novel
    Identification, Cloning, and Characterization of a Novel Soluble Receptor That Binds IL-22 and Neutralizes Its Activity1,2 Sergei V. Kotenko,3,4* Lara S. Izotova,* Olga V. Mirochnitchenko,* Elena Esterova,* Harold Dickensheets,† Raymond P. Donnelly,† and Sidney Pestka3* With the use of a partial sequence of the human genome, we identified a gene encoding a novel soluble receptor belonging to the class II cytokine receptor family. This gene is positioned on chromosome 6 in the vicinity of the IFNGR1 gene in a head-to-tail orientation. The gene consists of six exons and encodes a 231-aa protein with a 21-aa leader sequence. The secreted mature protein demonstrates 34% amino acid identity to the extracellular domain of the IL-22R1 chain. Cross-linking experiments demonstrate that the protein binds IL-22 and prevents binding of IL-22 to the functional cell surface IL-22R complex, which consists of two subunits, the IL-22R1 and the IL-10R2c chains. Moreover, this soluble receptor, designated IL-22-binding protein (BP), is capable of neutralizing IL-22 activity. In the presence of the IL-22BP, IL-22 is unable to induce Stat activation in IL-22-responsive human lung carcinoma A549 cells. IL-22BP also blocked induction of the suppressors of cytokine signaling-3 (SOCS-3) gene expression by IL-22 in HepG2 cells. To further evaluate IL-22BP action, we used hamster cells expressing a modified IL-22R complex ␥ consisting of the intact IL-10R2c and the chimeric IL-22R1/ R1 receptor in which the IL-22R1 intracellular domain was replaced with the IFN-␥R1 intracellular domain.
    [Show full text]
  • Brochure: Cytokine Atlas
    Cytokine Atlas First Edition Discover more at eBioscience.com Cytokines eBioscience, an Affymetrix company, is of cytokines as biomarkers has been adopted committed to developing and manufacturing due to their proven benefits as a means to high-quality, innovative reagents in an ISO understanding disease and therapies. Cytokines certified facility. As a provider of more than have expanded into specialized, disease 11,000 products, we empower our customers relevant panels for a more accurate assessment worldwide to obtain exceptional results by using of various diseases that include cardiovascular reagents that offer a new standard of excellence disease, asthma, inflammation, cancer, diabetes in quality, innovation and value. and rheumatoid arthritis. The Cytokine Atlas was developed as a resource guide to give a greater One key area of product focus is cytokines, understanding of the various cytokines and which are a large group of small signaling their roles in diseases. molecules that function extensively in cellular communication. Cytokines are most often associated with immune modulating molecules such as interleukins, chemokines, and interferons, but can also include other molecules. The use Abbreviations: Analyte Listing Key: APC Antigen Presenting Cell Purified Functional-Grade purified and non- CCL C-C motif chemokine conjugated antibodies Table of Contents CCR C-C chemokine receptor Violet Laser Antibodies conjugated to eFluor® 450 CD Cluster of Differentiation Blue Laser Antibodies conjugated to either FITC, Alexa Diseases 3 DC Dendritic Cell Fluor® 488, PE, PE-Cy5, PerCP-eFluor® 710, CMP Common Myloid Progenitor cell PerCP-Cy5.5, PE-Cy5.5, PE-Cy7 Cardiovascular Disease (CVD) . 3 CVD Cardiovascular Disease Red Laser Antibodies conjugated to either APC, Alexa CXCR C-X-C chemokine receptor Asthma/Airway Inflammation .
    [Show full text]
  • IL-19 Is a Component of the Pathogenetic IL-23/IL-17 Cascade
    ORIGINAL ARTICLE IL-19 Is a Component of the Pathogenetic IL-23/IL-17 Cascade in Psoriasis Ellen Witte1,2, Georgios Kokolakis1,2,KatrinWitte1,2,SandraPhilipp1,2, Wolf-Dietrich Doecke3, Nina Babel4,5,BiancaM.Wittig6, Katarzyna Warszawska1, Agata Kurek1,2, Magdalena Erdmann-Keding1,2, Stefanie Kunz1,2, Khusru Asadullah3,MarshallE.Kadin7, Hans-Dieter Volk4,8, Wolfram Sterry9, Kerstin Wolk1,2,10 and Robert Sabat1,2,10 Psoriasis is a common chronic inflammatory disease with characteristic skin alterations and functions as a model of immune-mediated disorders. Cytokines have a key role in psoriasis pathogenesis. Here, we demonstrated that out of 30 individually quantified cytokines, IL-19 showed the strongest differential expression between psoriatic lesions and healthy skin. Cutaneous IL-19 overproduction was reflected by elevated IL-19 blood levels that correlated with psoriasis severity. Accordingly, anti-psoriatic therapies substantially reduced both cutaneous and systemic IL-19 levels. IL-19 production was induced in keratinocytes by IL-17A and was further amplified by tumor necrosis factor-a and IL-22. Among skin cells, keratinocytes were found to be important targets of IL-19. IL-19 alone, however, regulated only a few keratinocyte functions. While increasing the production of S100A7/8/9 and, to a moderate extent, also IL-1b, IL-20, chemokine C-X-C motif ligand 8, and matrix metalloproteinase 1, IL-19 had no clear influence on the differentiation, proliferation, or migration of these cells. Importantly, IL-19 amplified many IL-17A effects on keratinocytes, including the induction of b-defensins, IL-19, IL-23p19, and T helper type 17- cell- and neutrophil-attracting chemokines.
    [Show full text]