Development of a novel treatment for inflammatory bowel disease via the regulation of the bacteria recognition system and effective molecules derived from bacteria

2009 Fiscal Year Final Research Report

• Project/Area Number: 19390194
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Asahikawa Medical College
• Principal Investigator: KOHGO Yutaka Asahikawa Medical College, 医学部, 教授 (10133183)
• Co-Investigator(Kenkyū-buntansha): ASHIDA Toshifumi 旭川医科大学, 医学部, 客員教授 (50261409) ; FUJIYA Mikihiro 旭川医科大学, 医学部, 准教授 (80322915) ; OHTAKE Takaaki 旭川医科大学, 医学部, 講師 (10359490) ; MAEMOTO Atsuo 旭川医科大学, 医学部, 客員准教授 (40400113)
• Project Period (FY): 2007 – 2009
• Keywords: 消化器学(食道,胃,小腸,大腸)

Research Abstract

The present study proposed a novel system of host-microbial interactions based on the sensing of bacterial secretions by epithelial membrane molecules such as transporters, leading to the maintenance of intestinal homeostasis. This novel system mainly mediates the interaction between the host and probitoics, including bacilli and lactobacilli. Conversely, this study also showed that human defensin (HD) 5 and 6, which are representative anti-microbial peptides secreted from the intestinal epithelia, possess an anti-inflammatory effect. Furthermore, HD-5 secretion was induced by isoleucine, which is an amino acid. The present study indicated that these effective molecules, including bacterial secretions, and HDs, and an amino acid (isoleucine), appear to be a novel potential compound for the treatment of intestinal disorders.

Research Products

• [Journal Article] Cytokine Regulation of OCTN2 Expression and Activity in Small and Large Intestine. (2011)
  • Author(s): Fujiya M, Inaba Y, Musch MW, Hu S, Kohgo Y, Chang EB
  • Journal Title: Inflammatory Bowel Diseases 17(4) Pages: 907-16
• [Journal Article] An unusual elevated lesion of the esophagus. (2011)
  • Author(s): Sawada K, Ikuta K, Itabashi K, Suzuki Y, Mizukami Y, Fujiya M, Kubo K, Tamura Y, Torimoto Y, Kohgo Y
  • Journal Title: Gut 60(4) Pages: 441
• [Journal Article] The expression of the anti-microbial peptide α-defensin/cryptdins in intestinal crypts decreases at the initial phase of intestinal inflammation in a model of inflammatory bowel disease, IL-10 deficient mice. (2010)
  • Author(s): Inaba Y, Ashida T, Ito T, Ishikawa C, Tanabe H, Maemoto A, Watari J, Ayabe T, Mizukami Y, Fujiya M, Kohgo Y
  • Journal Title: Inflammatory Bowel Diseases 16(9) Pages: 1488-95
• [Journal Article] Novel perspectives in probiotic treatment : The efficacy and unveiled mechanisms of the physiological functions. (2010)
  • Author(s): Fujiya M, Kohgo Y
  • Journal Title: Clin J Gastroenterol 3(Review) Pages: 117-127
• [Journal Article] Precursor Processing of Human Defensin-5 Is Essential to the Multiple Functions in vitro and in vivo. (2010)
  • Author(s): Ishikawa C, Tanabe H, Maemoto A, Ito T, Watari J, Kono T, Fujiya M, Ashida T, Ayabe T, Kohgo Y
  • Journal Title: J Innate Immunity 2 Pages: 66-76
• [Journal Article] Precursor Processing of Human Defensin-5 Is Essential to the Multiple Functions in vitro and in vivo. (2010)
  • Author(s): Ishikawa C, Maemoto A, Fujiya M, Ashida T, Kohgo Y
  • Journal Title: J Innate Immunity 2 Pages: 66-76
  • Peer Reviewed
• [Journal Article] 必須アミノ酸isoleucineによるhuman β defensin 2誘導に関する研究 (2010)
  • Author(s): 金野陽高
  • Journal Title: 北海道医学雑誌 85 Pages: 115-122
• [Journal Article] A Jak2 inhibitor, AG490, reverses lipin-1 suppression by TNF-alpha in 3T3-L1 adipocytes. (2009)
  • Author(s): Tsuchiya Y, Kohgo Y, Okumura T
  • Journal Title: Biochem Biophys Res Commun. 382(2) Pages: 348-52
  • Peer Reviewed
• [Journal Article] Functional role of metaplastic paneth cell defensins in Helicobacter pylori-infected stomach. (2008)
  • Author(s): Tanabe H, Maemoto A, Fijiya M, Ashida T, Kohgo Y
  • Journal Title: Helicobacter. 13(5) Pages: 70-9
  • Peer Reviewed
• [Journal Article] Disruption of the association of 73 kDa heat shock cognate protein with transporters associated with antigen processing (TAP) decreases TAP-dependent translocation of antigenic peptides into the endoplasmic reticulum. (2008)
  • Author(s): Kamiguchi K, Kohgo Y, Sato N
  • Journal Title: Microbiol Immunol. 52(2) Pages: 94-106
  • Peer Reviewed
• [Journal Article] Translational Inhibition of Colonic Epithelial Heat Shock Proteins by IFN-γ and TNF-α in Intestinal Inflammation. (2007)
  • Author(s): Hu S, Fujiya M, Chang EB
  • Journal Title: Gastroenterology 133(6) Pages: 1893-1904
  • Peer Reviewed
• [Journal Article] The Bacillus subtilis quorum-sensing molecule CSF contributes to intestinal homeostasis via OCTN2, a host cell membrane transporter. (2007)
  • Author(s): Fujiya M, Kohgo Y, Chang EB
  • Journal Title: Cell Host Microbe. 1(4) Pages: 299-308
  • Peer Reviewed
• [Journal Article] A diacylglycerol kinase inhibitor, R59022, stimulates glucose transport through a MKK3/6-p38 signaling pathway in skeletal muscle cells. (2007)
  • Author(s): Takahashi N, Kohgo Y, Okumura T
  • Journal Title: Biochem Biophys Res Commun. 360(1) Pages: 244-50
  • Peer Reviewed
• [Journal Article] Psoriasiform and pustular eruption induced by infliximab. (2007)
  • Author(s): Takahashi H, Ashida T, Kohgo Y, Iizuka H
  • Journal Title: J Dermatol. 34(7) Pages: 468-72
• [Journal Article] Denatured human alpha-defensin attenuates the bactericidal activity and the stability against enzymatic digestion. (2007)
  • Author(s): Tanabe H, Maemoto A, Ashida T, Kohgo Y
  • Journal Title: Biochem Biophys Res Commun. 358(1) Pages: 349-55
  • Peer Reviewed
• [Journal Article] Heat-killed body of Lactobacillus brevis SBC8803 ameliorates intestinal injury in a murine model of colitis by enhancing the intestinal barrier function.
  • Author(s): Ueno N, Fujiya M, Segawa S, Nata T, Moriichi K, Tanabe H, Mizukami Y, Kobayashi N, Ito K, Kohgo Y
  • Journal Title: Inflammatory Bowel Diseases (in press)
• [Presentation] Heat-Killed Body of Lactobacillus brevis SBC8803 Contributes to Maintain Intestinal Homeostasis and Improve Intestinal Injury in a Murine Model of Colitis. (2010)
  • Author(s): Ueno N, Fujiya M, Kohgo Y
  • Organizer: US-Japan GI Excutive meeting
  • Place of Presentation: Tokyo
  • Year and Date: 2010-06-18
• [Presentation] Competence and Sporulation Factor Derived From Bacillus Subtilis Improves Epithelial Cell Injury in Intestinal Inflammation via Immunomodulation and Cytoprotection. (2010)
  • Author(s): Okamoto K, Fujiva M, Nata T, Ueno N, Inaba Y, Ishikawa C, Ito T, Moriichi K, Tanabe H, Mizukami Y, Chang EB, Kohgo Y
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-05
• [Presentation] Heat-Killed Body of Lactobacillus brevis SBC8803 Contributes to Maintain Intestinal Homeostasis and Improve Intestinal Injury in a Murine Model of Colitis. (2010)
  • Author(s): Ueno N, Fujiya M, Segawa S, Nata T, Inaba Y, Moriichi K, Tanabe H, Mizukami Y, Kobayashi N, Ito K, Koheo Y
  • Organizer: DDW 2010 (AGA)
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-04
• [Presentation] Lactobacillus Brevis SBC8803 Culture Supernatant Induces Cytoprotective Small Heat Shock Protein HSP27 in Human Intestinal Epithelial CaCo2/Bbe Cells by ctivating the p38 MAPK Pathway and Alleviates DSS-Induced Acute Colitis in C57BL/6 Mice. (2010)
  • Author(s): Segawa S, Fujiya M, Ueno N, Kobayashi N, Ito K, Kohgo Y
  • Organizer: DDW 2010 (AGA)
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-04
• [Presentation] Heat-killed Lactobaccilus brevis SBC8803 improves intestinal injury in a murine model of colitis by protecting the intestinal epithelia and regulating pro-inflammatory cytokines. (2010)
  • Author(s): Ueno N, Fujiya M, Kohgo Y
  • Organizer: 2nd International Forum (Japanese Society of Gastroenterology)
  • Place of Presentation: Niigata
  • Year and Date: 2010-04-23
• [Presentation] Heat killed Lactobaccilus brevis SBC8803 improves intestinal injury in a murine model of colitis via the enhancement of the intestinal barrier function and the down-regulation of pro-inflammatory cytokines. (2010)
  • Author(s): Fujiya M, Ueno N, Segawa S, Nata T, Moriichi K, Tanabe H, Mizukami Y, Kobayashi N, Ito K, Kohgo Y
  • Organizer: The 4th Korea-Japan Inflammatory Bowel Disease Symposium
  • Place of Presentation: Tokyo
  • Year and Date: 2010-01-23
• [Presentation] Novel organic cation transporter 2 (OCTN2) transports probiotics-produced peptides and modulates intestinal homeostasis. (2007)
  • Author(s): Fujiya M, Kohgo Y
  • Organizer: 2007 US-Japan GI liver meeting.
  • Place of Presentation: Kyoto
  • Year and Date: 2007-06-22
• [Patent(Industrial Property Rights)] 腸管保護剤 (2011)
  • Inventor(s): 高後裕,藤谷幹浩,上野伸展,瀬川修一,小林直之
  • Industrial Property Rights Holder: 国立大学法人旭川医科大学,サッポロビール株式会社
  • Industrial Property Number: 特許権,PCT/JP2011/057689
  • Filing Date: 2011-03-28
• [Patent(Industrial Property Rights)] (2010)
  • Inventor(s): 高後裕,藤谷幹浩,上野伸展,瀬川修一,小林直之
  • Industrial Property Rights Holder: 国立大学法人旭川医科大学,サッポロビール株式会社
  • Patent Publication Number: 特許権,特開2010-083881
  • Acquisition Date: 2010-04-15