Analysis of transcriptional activation and isoforms of NF-IL6 in innate immunity

2008 Fiscal Year Final Research Report

• Project/Area Number: 19790358
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: UEMATSU Satoshi Osaka University, 微生物病研究所, 助教授 (50379088)
• Project Period (FY): 2007 – 2008
• Keywords: NF-IL6 / アイソフォーム / LAP / LIP / 細胞内寄生菌 / 細胞内殺菌 / 転写制御LPS誘導性遺伝子

Research Abstract

我々は転写因子NF-IL6の主要な転写活性化因子34 kDa LAPを欠如したKIマウス(C/ebpbM20A/M20AKIマウス)を作製して解析を行い、34 kDaのLAPは活性化したマクロファージにおいてNF-IL6による遺伝子誘導には必須であるが、細胞内寄生菌に対する殺菌には必要不可欠ではないことを明らかにした。また、転写抑制因子のLIPを欠如したノックインマウス(C/ebpbM151A/M151A KIマウス)を作製して解析を行い、LIPはin vivoにおいてLAPの機能を抑制しないことがわかった。

Research Products

• [Journal Article] Toll-Like 2 Receptor Mediates Apolipoprotein CIII-Induced Monocyte Activation (2008)
  • Author(s): Kawakami A, Osaka M, Aikawa M, Uematsu S, Akira S, Libby P, Shimokado K, Sacks FM, Yoshida M
  • Journal Title: Circ Res 103(12) Pages: 1402-1409
  • Peer Reviewed
• [Journal Article] Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production (2008)
  • Author(s): Saitoh T*, Fujita N*, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, Tsujimura T, Takeuchi O, Yoshimori T, Akira S
  • Journal Title: Nature 456(7219) Pages: 264-268
  • Peer Reviewed
• [Journal Article] Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines (2008)
  • Author(s): Zhu Q, Egelston C, Vivekanandhan A, Uematsu S, Akira S, Klinman DM, Belyakov IM, Berzofsky JA
  • Journal Title: Proc Natl Acad Sci U S A 105(42) Pages: 16260-16265
  • Peer Reviewed
• [Journal Article] Evidence for genes in addition to tlr7 in the yaa translocation linked with acceleration of systemic lupus erythematosus (2008)
  • Author(s): Santiago-Raber ML, Kikuchi S, Borel P, Uematsu S, Akira S, Kotzin BL, Izui S
  • Journal Title: J Immunol 181(2) Pages: 1556-1562
  • Peer Reviewed
• [Journal Article] Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 (2008)
  • Author(s): Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, Sato S, Tsujimura T, Yamamoto M, Yokota Y, Kiyono H, Miyasaka M, Ishii KJ, Akira S
  • Journal Title: Nat Immunol 9(7) Pages: 769-776
  • Peer Reviewed
• [Journal Article] Genetideletion of mPGES-1 accelerates intestinal tumorigenesis in APC(Min/+) mice (2008)
  • Author(s): Elander N, Ungerb?ck J, Olsson H, Uematsu S, Akira S, Soderkvist P
  • Journal Title: Biochem Biophys Res Commun 372(1) Pages: 249-253
  • Peer Reviewed
• [Journal Article] Cutting Edge: Overlapping Functions of TLR7 and TLR9 for Innate Defense against a Herpesvirus Infection (2008)
  • Author(s): Zucchini N, Bessou G, Traub S, Robbins SH, Uematsu S, Akira S, Alexopoulou L, Dalod M
  • Journal Title: J Immunol 180(9) Pages: 5799-5803
  • Peer Reviewed
• [Journal Article] Distinct roles for MyD88, TLR2, TLR5, and TLR9 in phagocytosis of Borrelia burgdorferi and inflammatory signaling (2008)
  • Author(s): Shin OS, Isberg R, Akira S, Uematsu S, Behera AK, Hu LT
  • Journal Title: Infect Immun 76(6) Pages: 2341-2351
  • Peer Reviewed
• [Journal Article] Selective synergy in anti-inflammatory cytokine production upon cooperated signaling via TLR4 and TLR2 in murine conventional dendritic cells (2008)
  • Author(s): Hirata N, Yanagawa Y, Ebihara T, Seya T, Uematsu S, Akira S, Hayashi F, IwabuK, Onoe K
  • Journal Title: Mol Immunol 45(10) Pages: 2734-2742
  • Peer Reviewed
• [Journal Article] TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines (2008)
  • Author(s): Ishii KJ, Kawagoe T, Koyama S, Matsui K, Kumar H, Kawai T, Uematsu S, Takeuchi O, Takeshita F, Coban C, Akira S
  • Journal Title: Nature 451(7179) Pages: 725-729
  • Peer Reviewed
• [Journal Article] TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity (2008)
  • Author(s): Zhang B, Ramesh G, Uematsu S, Akira S, Reeves WB
  • Journal Title: J Am Soc Nephrol 19(5) Pages: 923-932
  • Peer Reviewed
• [Journal Article] Induction of prostaglandin E(2) synthesis and microsomal prostaglandin E synthase-1 expression in murine microglia by glioma-derived soluble factors (2008)
  • Author(s): Nakano Y, Kuroda E, Kito T, Uematsu S, Akira S, Yokota A, Nishizawa S, Yamashita U
  • Journal Title: J Neurosurg 108(2) Pages: 311-319
  • Peer Reviewed
• [Journal Article] Colonic patches direct the cross-talk between systemic compartments and large intestine independently of innate immunity (2008)
  • Author(s): Chang SY, Cha HR, Uematsu S, Akira S, Igarashi O, Kiyono H, Kweon MN
  • Journal Title: J Immunol 180(3) Pages: 1609-1618
  • Peer Reviewed
• [Journal Article] TLR5KO mice have dysregulated intestinal gene expression and non-specific resistance to Salmonella-induced typhoid-like disease (2008)
  • Author(s): Vijay-Kumar M, Aitken JD, Kumar A, Neish AS, Uematsu S, Akira S, Gewirtz AT
  • Journal Title: Infect Immun 76(3) Pages: 1276-1281
  • Peer Reviewed
• [Journal Article] Toll-Like Receptors (TLRs) and Their Ligands (2008)
  • Author(s): Uematsu S, Akira S
  • Journal Title: Handb Exp Pharmacol 183 Pages: 1-20
  • Peer Reviewed
• [Journal Article] Association of microsomal prostaglandin E synthase 1 deficiency with impaired fracture healing, but not with bone loss or osteoarthritis, in mouse models of skeletal disorders (2007)
  • Author(s): Yamakawa K, Kamekura S, Kawamura N, Saegusa M, Kamei D, Murakami M, Kudo I, Uematsu S, Akira S, Chung UI, Nakamura K, Kawaguchi H
  • Journal Title: Arthritis Rheum 58(1) Pages: 172-183
  • Peer Reviewed
• [Journal Article] Activation of cytosolic phospholipase A2alpha in resident peritoneal macrophages by Listeria monocytogenes involves listeriolysin O and TLR2 (2007)
  • Author(s): Noor S, Goldfine H, Tucker DE, Suram S, Lenz LL, Akira S, Uematsu S, Girotti M, Bonventre JV, Breuel K, Williams DL, Leslie CC
  • Journal Title: J Biol Chem 283(8) Pages: 4744-4755
  • Peer Reviewed
• [Journal Article] Deletion of TLR5 results in spontaneous colitis in mice (2007)
  • Author(s): Vijay-Kumar M, Sanders CJ, Taylor RT, Kumar A, Aitken JD, Sitaraman SV, Neish AS, Uematsu S , Akira S, Williams IR, Gewirtz AT
  • Journal Title: J Clin Invest 117(12) Pages: 3909-3921
  • Peer Reviewed
• [Journal Article] Altered Inflammatory Responses in TLR5-Deficient Mice Infected with Legionella pneumophila (2007)
  • Author(s): Hawn TR, Berrington WR, Smith IA, Uematsu S, Akira S, Aderem A, Smith KD, Skerrett SJ
  • Journal Title: J Immunol 179(10) Pages: 6981-6987
  • Peer Reviewed
• [Journal Article] The C/EBPbeta Isoform 34-kDa LAP Is Responsible for NF-IL-6-Mediated Gene Induction in Activated Macrophages, but Is Not Essential for Intracellular Bacteria Killing (2007)
  • Author(s): Uematsu S, Kaisho T, Tanaka T, Matsumoto M, Yamakami M, Omori H, Yamamoto M, Yoshimori T, Akira S
  • Journal Title: J Immunol 179(8) Pages: 5378-5386
  • Peer Reviewed
• [Journal Article] Differential Role of TLR- and RLR-Signaling in the Immune Responses to Influenza A Virus Infection and Vaccination (2007)
  • Author(s): Koyama S, Ishii KJ, Kumar H, Tanimoto T, Coban C, Uematsu S, Kawai T, Akira S
  • Journal Title: J Immunol 179(7) Pages: 4711-4720
  • Peer Reviewed
• [Journal Article] Nitrogen dioxide promotes allergic sensitization to inhaled antigen (2007)
  • Author(s): Bevelander M, Mayette J, Whittaker LA, Paveglio SA, Jones CC, Robbins J, Hemenway D, Akira S, Uematsu S, Poynter ME
  • Journal Title: J Immunol 179(6) Pages: 3680-3688
  • Peer Reviewed
• [Journal Article] Enhanced TLR-mediated NF-IL6 dependent gene expression by Trib1 deficiency (2007)
  • Author(s): Yamamoto M, Uematsu S, Okamoto T, Matsuura Y, Sato S, Kumar H, Satoh T, Saitoh T, Takeda K, Ishii KJ, Takeuchi O, Kawai T, Akira S
  • Journal Title: J Exp Med 204(9) Pages: 2233-2239
  • Peer Reviewed
• [Journal Article] Lymphoma Immunotherapy with CpG Oligodeoxynucleotides Requires TLR9 Either in the Host or in the Tumor Itself (2007)
  • Author(s): Li J, Song W, Czerwinski DK, Varghese B, Uematsu S, Akira S, Krieg AM, Levy R
  • Journal Title: J Immunol 179(4) Pages: 2493-2500
  • Peer Reviewed
• [Journal Article] IL-3 is an important differentiation factor for the development of prostaglandin E(2)-producing macrophages between C57BL/6 and BALB/c mice (2007)
  • Author(s): Kuroda E, Noguchi J, Doi T, Uematsu S, Akira S, Yamashita U
  • Journal Title: Eur J Immunol 37(8) Pages: 2185-2195
  • Peer Reviewed
• [Journal Article] Blocking of the TLR5 Activation Domain Hampers Protective Potential of Flagellin DNA Vaccine (2007)
  • Author(s): Saha S, Takeshita F, Matsuda T, Jounai N, Kobiyama K, Matsumoto T, Sasaki S, Yoshida A, Xin KQ, Klinman DM, Uematsu S, Ishii KJ, Akira S, Okuda K
  • Journal Title: J Immunol 179(2) Pages: 1147-1154
  • Peer Reviewed
• [Journal Article] Immunogenicity and protective efficacy offered by a ribosomal-based vaccine from Shigella flexneri 2a (2007)
  • Author(s): Shim DH, Chang SY, Park SM, Jang H, Carbis R, Czerkinsky C, Uematsu S, Akira S, Kweon MN
  • Journal Title: Vaccine 25(25) Pages: 4828-4836
  • Peer Reviewed
• [Journal Article] Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice (2007)
  • Author(s): Ramesh G, Zhang B, Uematsu S, Akira S, Reeves WB
  • Journal Title: Am J Physiol Renal Physiol 293(1) Pages: 325-332
  • Peer Reviewed
• [Journal Article] Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor- mediated immune responses but not in TCR signaling (2007)
  • Author(s): Kawagoe T, Sato S, Jung A, Yamamoto M, Matsui K, Kato H, Uematsu S, Takeuchi O, Akira S
  • Journal Title: J Exp Med 204(5) Pages: 1013-1024
  • Peer Reviewed
• [Journal Article] Cutting Edge: Tlr5-/- Mice Are More Susceptible to Escherichia coli Urinary Tract Infection (2007)
  • Author(s): Andersen-Nissen E, Hawn TR, Smith KD, Nachman A, Lampano AE, Uematsu S, Akira S, Aderem A
  • Journal Title: J Immunol 178(8) Pages: 4717-4720
  • Peer Reviewed
• [Journal Article] Toll-like Receptors and Type I Interferons (2007)
  • Author(s): Uematsu S, Akira S
  • Journal Title: J Biol Chem 282(21) Pages: 15319-15323
  • Peer Reviewed
• [Presentation] Regulation of Humoral and Cellular Gut Immunity by Lamina Propria Dendritic Cells Expressing Toll-Like Receptor 5 (2008)
  • Author(s): 植松 智
  • Organizer: 第38回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-12-03
• [Presentation] Regulation of Humoral and Cellular Gut Immunity by Lamina Propria Dendritic Cells Expressing Toll-Like Receptor 5 (2008)
  • Author(s): 植松 智
  • Organizer: Toll 2008
  • Place of Presentation: Hotel Cascais Miragem
  • Year and Date: 2008-09-26
• [Presentation] 感染防御とTLR (2008)
  • Author(s): 植松 智
  • Organizer: 第2回移植医療のための次世代テクノロジー研究会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2008-09-19
• [Presentation] C/EBPb isoform, 34 kDa LAP is responsible for NF-IL6-mediated gene induction in activated macrophages but not essential for intracellular bacteria killing (2007)
  • Author(s): 植松 智
  • Organizer: 日本免疫学会総会
  • Place of Presentation: グランドプリンスホテル新高輪
  • Year and Date: 2007-11-21
• [Presentation] A new in vivo function of Toll-like receptor 5 in mouse small intestine (2007)
  • Author(s): 植松 智
  • Organizer: 国際粘膜免疫学会
  • Place of Presentation: 品川プリンスホテル
  • Year and Date: 2007-07-11
• [Presentation] 腸管におけるToll-like receptor 5の機能とSalmonella typhimurium感染における役割 (2007)
  • Author(s): 植松 智
  • Organizer: 第81回日本細菌学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2007-03-26