DOCSLIB.ORG

Human B Cells Expression in Terminally Differentiating Induces

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Human B Cells Expression in Terminally Differentiating Induces 1,25-Dihydroxyvitamin D3 Induces CCR10 Expression in Terminally Differentiating Human B Cells This information is current as Aiko-Konno Shirakawa, Daisuke Nagakubo, Kunio of September 28, 2021. Hieshima, Takashi Nakayama, Zhe Jin and Osamu Yoshie J Immunol 2008; 180:2786-2795; ; doi: 10.4049/jimmunol.180.5.2786 http://www.jimmunol.org/content/180/5/2786 Downloaded from References This article cites 55 articles, 29 of which you can access for free at: http://www.jimmunol.org/content/180/5/2786.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 28, 2021 *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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology 1,25-Dihydroxyvitamin D3 Induces CCR10 Expression in Terminally Differentiating Human B Cells1 Aiko-Konno Shirakawa,2 Daisuke Nagakubo,2 Kunio Hieshima, Takashi Nakayama, Zhe Jin, and Osamu Yoshie3 In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19؉ B cells into IgD؊CD38؉ plasma cells in vitro. A minor proportion of the ؉ ؊ ؉ resulting CD19 IgD CD38 cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active metabolite ؉ ؊ ؉ of vitamine D3, dramatically increased the proportion of CD19 IgD CD38 cells expressing high levels of CCR10. The 1,25- ؉ ؉ (OH)2D3 also increased the number of CCR10 cells expressing surface IgA, although the majority of CCR10 cells remained Downloaded from negative for surface IgA. Thus, 1,25-(OH)2D3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)2D3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)2D3.We confirmed the specific binding of Ets-1 and 1,25-(OH)2D3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)2D3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human http://www.jimmunol.org/ CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)2D3. The Journal of Immunology, 2008, 180: 2786–2795. lasma cells represent the terminal stage of B cell differ- gration and tissue localization of lymphocytic cells (2, 4). As for entiation and secrete large amounts of Ab. The transcrip- plasma cells, CXCR4 has been demonstrated to guide the move- P tion factors Blimp-1 and XBP-1 play essential roles in the ment of plasma cells to splenic red pulp, lymph node medullary plasma cell differentiation and function (1). Plasma cells exhibit cords, and bone marrow, where its ligand CXCL12 is abundantly preferential tissue localization in accordance with the route of im- produced (5). CXCR3 mobilizes IgG-secreting plasma cells to in- munization and the isotypes of Ig secreted. IgG-secreting plasma flammatory sites, where its ligands CXCL9, CXCL10, and/or by guest on September 28, 2021 cells are mainly induced by a systemic route of immunization and CXCL11 are strongly up-regulated (6–8). CCR9 contributes to the preferentially localize in the bone marrow. In contrast, IgA-secret- localization of IgA-secreting plasma cells to the small intestine ing plasma cells are predominantly induced by a mucosal route of (9–11), where its ligand CCL25 is selectively produced by the immunization and preferentially localize in the mucosal tissues (2). intestinal epithelial cells (11–13). Differential expression of tissue-specific adhesion molecules has CCR10 was originally identified as the receptor for CCL27 (14), 4 been demonstrated in Ab-secreting cells (ASCs) depending on the which is selectively expressed by epidermal keratinocytes (15, 16). route of immunization (3). Recently, chemokines and their recep- Accordingly, CCR10 has been shown to be expressed by skin- tors have been attracting much attention as the regulators of mi- homing effector/memory T cells expressing cutaneous lymphocyte Ag (14, 17, 18). Subsequently, another ligand of CCR10 was iden- tified and termed CCL28, which is widely expressed by the Department of Microbiology, Kinki University School of Medicine, Osaka-Sayama, epithelial cells of various mucosal tissues (11, 19–21). Thus, cer- Osaka, Japan tain types of CCR10-expressing cells must be present in the mu- Received for publication November 29, 2006. Accepted for publication December 13, 2007. cosal tissues. Previously, we have demonstrated that EBV-immor- talized human B cells express CCR10, although CCR10 is not The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance inducible by EBV-encoded latent genes (22). This was rather un- with 18 U.S.C. Section 1734 solely to indicate this fact. expected because the expression of CCR10 had not been described 1 This work was supported by a grant-in-aid from the Ministry of Education, Culture, at any of the developmental or differentiation stages of B cells Sports and Technology, Japan; by Solution-Oriented Research for Science and Tech- nology from the Japan Science and Technology Corporation; and by the High-Tech examined to date (23). Because EBV-immortalized B cells resem- Research Center Project for Private Universities: matching fund subsidy from the ble plasma cells in terms of the continuous production of Igs (24), Ministry of Education, Culture, Sports, Science and Technology of Japan, 2002–2009. we hypothesized that CCR10 might be selectively expressed at the 2 A.-K.S. and D.N. contributed equally to this work. terminal differentiation stage of B cells. We have indeed demon- 3 Address correspondence and reprint requests to Dr. Osamu Yoshie, Department of strated that a substantial fraction of plasma cells derived from hu- Microbiology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka- Sayama, Osaka 589-8511, Japan. E-mail address: [email protected] man bone marrow expresses CCR10 and efficiently migrates to its 4 ligands CCL27 and CCL28 (25). Furthermore, Butcher and his Abbreviations used in this paper: ASC, Ab-secreting cell; 1,25-(OH)2D3, 1,25-di- hydroxyvitamin D3; DC, dendritic cell; GALT, gut-associated lymphoid tissue; HEK, colleagues (26, 27) have demonstrated that IgA-ASCs present in human embryonic kidney; LCL, lymphoblastoid cell line; RA, all-trans retinoic acid; various mucosal tissues commonly express CCR10. We have also VDR, vitamin D receptor; VDRE, vitamin D response element. demonstrated that CCR10 plays an important role in the homing of Copyright © 2008 by The American Association of Immunologists, Inc. 0022-1767/08/$2.00 IgA-ASCs into the small intestine and colon (11). Consequently, it www.jimmunol.org The Journal of Immunology 2787 is now considered that the CCL28-CCR10 system comprises an Systems and Jackson ImmunoResearch Laboratories, respectively. The important element in the common mucosal immune system by pro- 1,25-(OH)2D3 was purchased from Cayman Chemical. All-trans retinoic acid (RA) was purchased from Sigma-Aldrich. 22-Oxa-1,25-(OH) D moting the wide distribution of locally induced IgA-ASCs to var- 2 3 (OCT), an analog of 1,25-(OH)2D3 and a VDR agonist, was provided by ious mucosal tissues in the body (2). However, the regulatory Chugai Pharmaceutical. TEI-9647, a VDR antagonist, was provided by mechanism of CCR10 expression in terminally differentiating B Teijin Institute for Bio-Medical Research. Unused transfusion blood sam- cells has not been determined yet. ples were provided by Osaka Red Cross Hospital. The use of the blood The 1,25-dihydroxyvitamin D (1,25-(OH) D ) is the biologi- samples was approved by the ethical committee of Kinki University School 3 2 3 of Medicine. PBMC were prepared using Ficoll-Paque. CD19ϩ B cells cally active metabolite of vitamin D3, which binds and activates were purified from PBMC by negative selection using BD IMag Human B the nuclear vitamin D receptor (VDR). The activated VDR dimer- Lymphocyte Enrichment Set-DM and BD IMagnet (BD Biosciences). The izes with another nuclear receptor, one of the retinoid X receptors, preparations were typically Ͼ90% CD19ϩ B cells. Induction of B cell and the heterodimer binds with high affinity to vitamin D response differentiation into plasma cells was performed essentially as described previously (36). Briefly, purified CD19ϩ B cells were cultured in the pres- elements (VDREs) in the promoter region of target genes (28). Ј ␮ ␮ ence of anti-IgM F(ab )2 at 5 g/ml, anti-CD40 at 1 g/ml, and IL-21 at Besides the role in calcium homeostasis, 1,25-(OH)2D3 is also 100 ng/ml for 6 days. On day 3, 1,25-(OH)2D3, OCT, TEI-9647, and RA known to exert potent immunomodulatory activities (29–31).
Load more

Recommended publications
  • Induces Homing of Antigen-Specific and Non Chemokine-Adjuvanted
    Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non −Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae This information is current as of September 25, 2021. Yoann Aldon, Sven Kratochvil, Robin J. Shattock and Paul F. McKay J Immunol published online 8 January 2020 http://www.jimmunol.org/content/early/2020/01/07/jimmun ol.1901184 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2020/01/07/jimmunol.190118 Material 4.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 25, 2021 *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 Author Choice Freely available online through The Journal of Immunology Author Choice option 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 © 2020 The Authors All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published January 8, 2020, doi:10.4049/jimmunol.1901184 The Journal of Immunology Chemokine-Adjuvanted Plasmid DNA Induces Homing of Antigen-Specific and Non–Antigen-Specific B and T Cells to the Intestinal and Genital Mucosae Yoann Aldon, Sven Kratochvil, Robin J.
    [Show full text]
  • Antimicrobial Activity As a Chemokine with Broad-Spectrum CCL28 Has
    CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity This information is current as Kunio Hieshima, Haruo Ohtani, Michiko Shibano, Dai of September 26, 2021. Izawa, Takashi Nakayama, Yuri Kawasaki, Fumio Shiba, Mitsuru Shiota, Fuminori Katou, Takuya Saito and Osamu Yoshie J Immunol 2003; 170:1452-1461; ; doi: 10.4049/jimmunol.170.3.1452 Downloaded from http://www.jimmunol.org/content/170/3/1452 References This article cites 36 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/170/3/1452.full#ref-list-1 http://www.jimmunol.org/ 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 26, 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 © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CCL28 Has Dual Roles in Mucosal Immunity as a Chemokine with Broad-Spectrum Antimicrobial Activity1 Kunio Hieshima,* Haruo Ohtani,2‡ Michiko Shibano,* Dai Izawa,* Takashi Nakayama,* Yuri Kawasaki,* Fumio Shiba,* Mitsuru Shiota,† Fuminori Katou,§ Takuya Saito,¶ and Osamu Yoshie3* CCL28 is a CC chemokine signaling via CCR10 and CCR3 that is selectively expressed in certain mucosal tissues such as exocrine glands, trachea, and colon.
    [Show full text]
  • The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature
    International Journal of Molecular Sciences Review The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature Jan Korbecki 1 , Klaudyna Kojder 2, Patrycja Kapczuk 1, Patrycja Kupnicka 1 , Barbara Gawro ´nska-Szklarz 3 , Izabela Gutowska 4 , Dariusz Chlubek 1 and Irena Baranowska-Bosiacka 1,* 1 Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] (J.K.); [email protected] (P.K.); [email protected] (P.K.); [email protected] (D.C.) 2 Department of Anaesthesiology and Intensive Care, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-281 Szczecin, Poland; [email protected] 3 Department of Pharmacokinetics and Therapeutic Drug Monitoring, Pomeranian Medical University in Szczecin, Powsta´nców Wielkopolskich 72 Av., 70-111 Szczecin, Poland; [email protected] 4 Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Powsta´nców Wlkp. 72 Av., 70-111 Szczecin, Poland; [email protected] * Correspondence: [email protected]; Tel.: +48-914661515 Abstract: Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influ- ence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 Citation: Korbecki, J.; Kojder, K.; Kapczuk, P.; Kupnicka, P.; (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors— Gawro´nska-Szklarz,B.; Gutowska, I.; CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8.
    [Show full text]
  • The Chemokine System in Innate Immunity
    Downloaded from http://cshperspectives.cshlp.org/ on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press The Chemokine System in Innate Immunity Caroline L. Sokol and Andrew D. Luster Center for Immunology & Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114 Correspondence: [email protected] Chemokines are chemotactic cytokines that control the migration and positioning of immune cells in tissues and are critical for the function of the innate immune system. Chemokines control the release of innate immune cells from the bone marrow during homeostasis as well as in response to infection and inflammation. Theyalso recruit innate immune effectors out of the circulation and into the tissue where, in collaboration with other chemoattractants, they guide these cells to the very sites of tissue injury. Chemokine function is also critical for the positioning of innate immune sentinels in peripheral tissue and then, following innate immune activation, guiding these activated cells to the draining lymph node to initiate and imprint an adaptive immune response. In this review, we will highlight recent advances in understanding how chemokine function regulates the movement and positioning of innate immune cells at homeostasis and in response to acute inflammation, and then we will review how chemokine-mediated innate immune cell trafficking plays an essential role in linking the innate and adaptive immune responses. hemokines are chemotactic cytokines that with emphasis placed on its role in the innate Ccontrol cell migration and cell positioning immune system. throughout development, homeostasis, and in- flammation. The immune system, which is de- pendent on the coordinated migration of cells, CHEMOKINES AND CHEMOKINE RECEPTORS is particularly dependent on chemokines for its function.
    [Show full text]
  • Immune Evasion by Murine Melanoma Mediated Through CC Chemokine
    Immune Evasion by Murine Melanoma Mediated through CC Chemokine Receptor-10 Takashi Murakami,1 Adela R. Cardones,1 Steven E. Finkelstein,2 Nicholas P. Restifo,2 Brenda A. Klaunberg,5 Frank O. Nestle,4 S. Sianna Castillo,3 Phillip A. Dennis,3 and Sam T. Hwang1 1Dermatology, 2Surgery, and 3Cancer Therapeutics Branches, CCR, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892 4National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892 5Department of Dermatology, University of Zürich Hospital, CH-8091 Zürich, Switzerland Abstract Human melanoma cells frequently express CC chemokine receptor (CCR)10, a receptor whose ligand (CCL27) is constitutively produced by keratinocytes. Compared with B16 murine melanoma, cells rendered more immunogenic via overexpression of luciferase, B16 cells that overexpressed both luciferase and CCR10 resisted host immune responses and readily formed tumors. In vitro, exposure of tumor cells to CCL27 led to rapid activation of Akt, resistance to cell death induced by melanoma antigen-specific cytotoxic T cells, and phosphatidylinositol-3- kinase (PI3K)–dependent protection from apoptosis induced by Fas cross-linking. In vivo, cutaneous injection of neutralizing antibodies to endogenous CCL27 blocked growth of CCR10-expressing melanoma cells. We propose that CCR10 engagement by locally produced CCL27 allows melanoma cells to escape host immune antitumor killing mechanisms (possibly through activation of PI3K/Akt), thereby providing a means for tumor progression. Key words: metastasis • chemokine receptor • cancer • cell signaling Introduction Malignant melanoma is a potentially fatal skin cancer that is In this paper, we explore the role of chemokine recep- increasing in incidence (1). The ability of tumor cells to tors in the context of tumor escape from immune cell avoid immune surveillance is likely to be central to the clearance mechanisms.
    [Show full text]
  • Chloride Channels Regulate Differentiation and Barrier Functions
    RESEARCH ARTICLE Chloride channels regulate differentiation and barrier functions of the mammalian airway Mu He1†*, Bing Wu2†, Wenlei Ye1, Daniel D Le2, Adriane W Sinclair3,4, Valeria Padovano5, Yuzhang Chen6, Ke-Xin Li1, Rene Sit2, Michelle Tan2, Michael J Caplan5, Norma Neff2, Yuh Nung Jan1,7,8, Spyros Darmanis2*, Lily Yeh Jan1,7,8* 1Department of Physiology, University of California, San Francisco, San Francisco, United States; 2Chan Zuckerberg Biohub, San Francisco, United States; 3Department of Urology, University of California, San Francisco, San Francisco, United States; 4Division of Pediatric Urology, University of California, San Francisco, Benioff Children’s Hospital, San Francisco, United States; 5Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Heaven, United States; 6Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, United States; 7Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; 8Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States *For correspondence: Abstract The conducting airway forms a protective mucosal barrier and is the primary target of [email protected] (MH); [email protected] airway disorders. The molecular events required for the formation and function of the airway (SD); mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway [email protected] (LYJ) diseases,
    [Show full text]
  • CCL28 a Mucosal Chemokine That Has a Protective Role in the MALT
    UC Irvine UC Irvine Electronic Theses and Dissertations Title Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation Permalink https://escholarship.org/uc/item/2m7018vx Author Vazquez, Monica Ivonne Publication Date 2015 Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, IRVINE Functional Characterization of IL-40 a novel B cell cytokine and Physiological Implications of CCL28 ablation DISSERTATION Submitted in Partial Satisfaction of the Requirements for the Degree of DOCTOR OF PHILOSOPHY In Biomedical Sciences By Monica Ivonne Vazquez Dissertation Committee: Professor Albert Zlotnik, Chair Professor Kenneth J. Longmuir Professor Craig M. Walsh 2015 Portions of Chapter 1 © 2015 Elselvier Ltd. All other chapters © 2015 Monica Ivonne Vazquez DEDICATION TO My husband Brian Vazquez And son Isaiah Vazquez They have been part of my entire life as a student from my undergraduate years to my graduate career. They both provided a much needed sense of balance and always brought me back to what matters the most: Family. My little girl, Penelope, who always brings a smile to face and has given me the strength to continue. Getsemani, expected April 7, 2015, who I cannot wait to meet. Thank you for your unending love and support. ii TABLE OF CONTENTS Page LIST OF FIGURES iv-vi LIST OF TABLES vii ACKNOWLEDGMENTS viii CURRICULUM VITAE ix-x LIST OF ABBREVIATIONS xi-xiv ABSTRACT OF THE DISSERTATION xv-xvi Chapter
    [Show full text]
  • Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1
    pathogens Article Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1 Acacia F. Dishman 1,2,†, Jie He 3,†, Brian F. Volkman 1,* and Anna R. Huppler 3,* 1 Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] 2 Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA 3 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] * Correspondence: [email protected] (B.F.V.); [email protected] (A.R.H.) † These authors contributed equally. Abstract: Candida species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, antimicrobial chemokine that interconverts between the conserved chemokine fold (an α–β monomer) and an alternate fold (an all-β dimer). Previous work has shown that human XCL1 kills C. albicans but has not assessed whether one or both XCL1 folds perform this activity. Here, we use structurally locked engineered XCL1 variants and Candida killing assays, adenylate kinase release assays, and propidium iodide uptake assays to demonstrate that both XCL1 folds kill Candida, but they do so via different mechanisms. Our results suggest that the alternate fold kills via membrane disruption, consistent with previous work, and the chemokine fold does not. XCL1 fold-switching thus provides a mechanism to regulate Citation: Dishman, A.F.; He, J.; the XCL1 mode of antifungal killing, which could protect surrounding tissue from damage associ- Volkman, B.F.; Huppler, A.R.
    [Show full text]
  • Role of Chemokines in Hepatocellular Carcinoma (Review)
    ONCOLOGY REPORTS 45: 809-823, 2021 Role of chemokines in hepatocellular carcinoma (Review) DONGDONG XUE1*, YA ZHENG2*, JUNYE WEN1, JINGZHAO HAN1, HONGFANG TUO1, YIFAN LIU1 and YANHUI PENG1 1Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei 050051; 2Medical Center Laboratory, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, P.R. China Received September 5, 2020; Accepted December 4, 2020 DOI: 10.3892/or.2020.7906 Abstract. Hepatocellular carcinoma (HCC) is a prevalent 1. Introduction malignant tumor worldwide, with an unsatisfactory prognosis, although treatments are improving. One of the main challenges Hepatocellular carcinoma (HCC) is the sixth most common for the treatment of HCC is the prevention or management type of cancer worldwide and the third leading cause of of recurrence and metastasis of HCC. It has been found that cancer-associated death (1). Most patients cannot undergo chemokines and their receptors serve a pivotal role in HCC radical surgery due to the presence of intrahepatic or distant progression. In the present review, the literature on the multi- organ metastases, and at present, the primary treatment methods factorial roles of exosomes in HCC from PubMed, Cochrane for HCC include surgery, local ablation therapy and radiation library and Embase were obtained, with a specific focus on intervention (2). These methods allow for effective treatment the functions and mechanisms of chemokines in HCC. To and management of patients with HCC during the early stages, date, >50 chemokines have been found, which can be divided with 5-year survival rates as high as 70% (3). Despite the into four families: CXC, CX3C, CC and XC, according to the continuous development of traditional treatment methods, the different positions of the conserved N-terminal cysteine resi- issue of recurrence and metastasis of HCC, causing adverse dues.
    [Show full text]
  • Epithelial Inflammation Is Associated with CCL28 Production and the Recruitment of Regulatory T Cells Expressing CCR10
    Epithelial Inflammation Is Associated with CCL28 Production and the Recruitment of Regulatory T Cells Expressing CCR10 This information is current as Bertus Eksteen, Alice Miles, Stuart M. Curbishley, Chris of September 26, 2021. Tselepis, Allister J. Grant, Lucy S. K. Walker and David H. Adams J Immunol 2006; 177:593-603; ; doi: 10.4049/jimmunol.177.1.593 http://www.jimmunol.org/content/177/1/593 Downloaded from References This article cites 51 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/177/1/593.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • 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 by guest on September 26, 2021 *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 © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Epithelial Inflammation Is Associated with CCL28 Production and the Recruitment of Regulatory T Cells Expressing CCR101 Bertus Eksteen,* Alice Miles,* Stuart M. Curbishley,* Chris Tselepis,‡ Allister J.
    [Show full text]
  • Ccl27/Ccl2 Ccl28
    UNIVERSITY OF CALIFORNIA, SAN DIEGO Structural and Functional Analysis of the Chemokine CCL27 and the Expression and Purification of Silent Chemokine Receptors D6 and DARC A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Chemistry and Biochemistry by Ariane L. Jansma Committee in charge: Professor Tracy M. Handel, Chair Professor Patricia Jennings, Co-Chair Professor William Gerwick Professor Susan Taylor Asst. Professor Faik A. Tezcan 2009 This Dissertation of Ariane L. Jansma is approved, and it is acceptable in quality and form for publication on microfilm and electronically: ________________________________________________________ ________________________________________________________ ________________________________________________________ ________________________________________________________ Co-Chair ________________________________________________________ Chair iv TABLE OF CONTENTS Signature Page ................................................................................................................ iii Table of Contents............................................................................................................. iv List of Figures.................................................................................................................... x List of Tables...................................................................................................................xiii List of Abbreviations........................................................................................................xiv
    [Show full text]
  • A Novel Role for Constitutively Expressed Epithelial-Derived Chemokines As Antibacterial Peptides in the Intestinal Mucosa
    ARTICLES nature publishing group A novel role for constitutively expressed epithelial-derived chemokines as antibacterial peptides in the intestinal mucosa K K o t a r s k y 1 , K M S i t n i k 1 , H S t e n s t a d 1 , H K o t a r s k y 2 , A S c h m i d t c h e n 3 , M K o s l o w s k i 4 , J We h k a m p 4 a n d W W A g a c e 1 Intestinal-derived chemokines have a central role in orchestrating immune cell influx into the normal and inflamed intestine. Here, we identify the chemokine CCL6 as one of the most abundant chemokines constitutively expressed by both murine small intestinal and colonic epithelial cells. CCL6 protein localized to crypt epithelial cells, was detected in the gut lumen and reached high concentrations at the mucosal surface. Its expression was further enhanced in the small intestine following in vivo administration of LPS or after stimulation of the small intestinal epithelial cell line, mICc12 , with IFN , IL-4 or TNF . Recombinant- and intestinal-derived CCL6 bound to a subset of the intestinal microflora and displayed antibacterial activity. Finally, the human homologs to CCL6, CCL14 and CCL15 were also constitutively expressed at high levels in human intestinal epithelium, were further enhanced in inflammatory bowel disease and displayed similar antibacterial activity. These findings identify a novel role for constitutively expressed, epithelial-derived chemokines as antimicrobial peptides in the intestinal mucosa.
    [Show full text]