Negative regulation of TLR signaling by G-CSF and ATP in leukocytes

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka City University
• Principal Investigator: KITAGAWA Seiichi 大阪市立大学, 医学(系)研究科(研究院), 教授 (50133278)
• Co-Investigator(Kenkyū-buntansha): KATO Takayuki 大阪市立大学, 大学院医学研究科, 講師 (50343413)
• Project Period (FY): 2011 – 2013
• Keywords: 好中球 / 単球 / リポポリサッカライド / 腫瘍壊死因子α / 顆粒球コロニー刺激因子 / ATP / インターフェロンγ / IL-8

Research Abstract

Various Toll-like receptors are expressed on human leukocytes such as neutrophils and monocytes, and play an important role in the innate immunity. Although the molecular mechanisms of Toll-like receptor-mediated cell activation have been increasingly understood, the positive and negative regulatory mechanisms on this system remain to be elusive. To elucidate the negative regulatory mechanisms by physiological molecules is particularly important for possible treatment of inflammation and tissue damage. We found that this system was positively regulated by granulocyte-macrophage colony-stimulating factor, interferon-alpha and interferon-gamma, and was negatively regulated by granulocyte colony-stimulating factor and ATP (adenosine tri-phosphate).

Research Products

• [Journal Article] Isolation of diploid baker's yeast capable of strongly activating immune cells and analyses of the cell wall structure (2014)
  • Author(s): Takada Y, Mizobuchi A, Kato T, Kasahara E, Ito C, Watanabe H, Kanzaki K, Kitagawa S, Tachibana T, Azuma M
  • Journal Title: Bioscience, Biotechnology and Biochemistr Volume: (in press)
  • Peer Reviewed
• [Journal Article] Gender difference in tumor necrosis factor-αproduction in human neutrophils stimulated by lipopolysaccharide and interferon-γ (2013)
  • Author(s): Aomatsu M, Kato T, Kasahara E, Kitagawa S
  • Journal Title: Biochem Biophys Res Commun Volume: 441 Pages: 220-225
  • DOI: 10.1016/j.bbrc.2013.10.042
  • Peer Reviewed
• [Journal Article] Heterogeneous nuclear ribonucleoprotein Q is a novel substrate of SH2 domain-containing phosphatase-2 (2013)
  • Author(s): Watanabe N, Kato T, Fujita H, Kitagawa S
  • Journal Title: J Biochem Volume: 154 Pages: 475-480
  • DOI: 10.1093/jb/mvt078
  • Peer Reviewed
• [Journal Article] Adjunctive imprint cytology of core needle biopsy specimens improved diagnostic accuracy for breast cancer (2013)
  • Author(s): Kashiwagi S, Onoda N, Asano Y, Noda S, Kawajiri H, Takashima T, Ohsawa M, Kitagawa S, Hirakawa K.
  • Journal Title: Springerplus Volume: 2 Pages: 372
  • DOI: 10.1186/2193-1801-2-372
  • Peer Reviewed
• [Journal Article] Clinical significance of the sub-classification of 71 cases mucinous breast carcinoma (2013)
  • Author(s): Kashiwagi S, Onoda N, Asano Y, Noda S, Kawajiri H, Takashima T, Ohsawa M, Kitagawa S, Hirakawa K
  • Journal Title: Springerplus Volume: 2 Pages: 481
  • DOI: 10.1186/2193-1801-2-481
  • Peer Reviewed
• [Journal Article] S1-1/RBM10: Multiplicity and cooperativity of nuclear localization domains (2013)
  • Author(s): Xiao S, Wang L, Kimura M, Kojima H, Kunimoto H, Nishiumi F, Yamamoto N, Nishio K, Fujimoto S, Kato T, Kitagawa S, Yamane H, Nakajima K, Inoue A
  • Journal Title: Biol Cell Volume: 105 Pages: 162-174
  • DOI: 10.1111/boc.201200068
  • Peer Reviewed
• [Journal Article] 食細胞の機能とサイトカイン (2012)
  • Author(s): 北川誠一
  • Journal Title: 臨床免疫・アレルギー科, (依頼原稿) Volume: 57 (Suppl. 21) Pages: 698-706
• [Journal Article] Stimulation of human formyl peptide receptors by calpain inhibitors : Homology modeling of receptors and ligand docking simulation (2011)
  • Author(s): Fujita H, Kato T, Watanabe N, Takahashi T, Kitagawa S
  • Journal Title: Arch Biochem Biophys Volume: 516 Pages: 121-127
  • DOI: 10.1016/j.abb.2011.09.017
  • Peer Reviewed
• [Journal Article] Shared and distinct functions of the transcription factors IRF4 and IRF8 in myeloid cell development (2011)
  • Author(s): Yamamoto M, Kato T, Hotta C, Nishiyama A, Kurotaki D, Yoshinari M, Takami M, Ichino M, Nakazawa M, Matsuyama T, Kamijo R, Kitagawa S, Ozato K, Tamura T
  • Journal Title: PLoS ONE Volume: 6 Pages: e25812
  • DOI: 10.1371/journal.pone.0025812
  • Peer Reviewed
• [Journal Article] Calpain inhibitors stimulate phagocyte functions via activation of human formyl peptide receptors (2011)
  • Author(s): Fujita H, Kato T, Watanabe N, Takahashi T, Kitagawa S
  • Journal Title: Arch Biochem Biophys Volume: 513 Pages: 51-60
  • DOI: 10.1016/j.abb.2011.06.007
  • Peer Reviewed
• [Presentation] Regulation of G-CSF/IFN/ATP on LPS-induced TNF-αproduction in human neutrophils (2013)
  • Author(s): 加藤隆幸、青松恵美、笠原恵美子、藤田寿一、北川誠一
  • Organizer: 第75回日本血液学会学術集会, (優秀ポスター賞)
  • Place of Presentation: 札幌市教育文化会館,札幌
  • Year and Date: 20131011-13
• [Presentation] Role of the HPA-axis and mitochondria in LPS-induced septic shock (2013)
  • Author(s): Kasahara E, Sekiyama A, Hori M, Chida D, Okamura H, Inoue M, Kitagawa S
  • Organizer: 6th Joint Meeting of the Societies for Free Radical Research
  • Place of Presentation: Mercure Sydney Hotel, Sydney, Australia
  • Year and Date: 20130912-14
  • Invited
• [Presentation] LPSおよびIFN-γ刺激により誘導されるヒト好中球からのTNF-α産生における性差 (2013)
  • Author(s): 青松恵美、加藤隆幸、笠原恵美子、北川誠一
  • Organizer: 第106回近畿生理学談話会
  • Place of Presentation: 奈良県立医科大学,奈良
  • Year and Date: 2013-11-02
• [Presentation] Activation of human formyl peptide receptors by calpain inhibitors (2012)
  • Author(s): 藤田寿一、加藤隆幸、渡邊哲史、高橋達治、北川誠一
  • Organizer: 第74回日本血液学会学術集会, (優秀ポスター賞)
  • Place of Presentation: 京都国際会館,京都
  • Year and Date: 20121019-21
• [Presentation] Stimulation of human formyl peptide receptors by calpain inhibitors (2012)
  • Author(s): Fujita H, Kato T, Watanabe N, Takahashi T, Kitagawa S
  • Organizer: 5th Anniversary of Protein and Peptide Conference (PepCon-2012)
  • Place of Presentation: Beijing, China
  • Year and Date: 2012-03-25
  • Invited
• [Presentation] ヒト・フォルミルペプチド受容体を介したカルパイン阻害剤による細胞機能の活性化 (2011)
  • Author(s): 藤田寿一、加藤隆幸、渡邊哲史、高橋達治、北川誠一
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場,名古屋
  • Year and Date: 20111014-16
• [Presentation] マクロファージのLPS応答におけるミトコンドリアの役割 (2011)
  • Author(s): 笠原恵美子、関山敦生、堀美香、松本壮吉、佐藤英介、岡村春樹、井上正康、北川誠一
  • Organizer: 第84回日本生化学会
  • Place of Presentation: 京都国際会館,京都
  • Year and Date: 20110921-24
• [Presentation] Negative regulation of G-CSF on TLR agonist-induced TNF production in human monocytes and neutrophils (2011)
  • Author(s): Kato T, Fujita H, Watanabe N, Kitagawa S
  • Organizer: 13th International TNF Conference (TNF2011)
  • Place of Presentation: Hyogo, Japan
  • Year and Date: 2011-05-16
• [Book] Biological Effects of Calpain Inhibitors on Human Phagocyte Functions. In : Enzymes and Enzyme Activity, (Chapter V. ed. E.M. Lashinski) (2013)
  • Author(s): Kitagawa S, Kato T, Kitagawa M, Aomatsu M, Fujita H
  • Total Pages: 121-144, 185
  • Publisher: Nova Science Publishers, Inc. NY
• [Book] 血液細胞の産生, 鉄の代謝, 白血球の生理学, 血小板の生理学と凝固機能, 血液型, 標準生理学.第8版 (2013)
  • Author(s): 北川誠一, (小澤瀞司、福田康一郎監修)
  • Total Pages: 508-511, 522-523, 525-531, 538-540, 541-543, 1140
  • Publisher: 医学書院, (東京)
• [Book] 免疫、感染、炎症, ギャノング生理学.原書24版 (2013)
  • Author(s): 北川誠一, (岡田泰伸監訳)
  • Total Pages: 77-96, 860
  • Publisher: 丸善出版, (東京)
• [Book] Visual Basic Medicine, 2nd edition, Institute of A-V Medical Education, Inc (2011)
  • Author(s): Kitagawa S
  • Total Pages: 10
  • Publisher: Blood, (Tokyo, DVD Text)