Elucidation of mechanism of cytomegalovirus reactivation and infection in inflammatory bowel disease.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590810
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto University
• Principal Investigator: NAKASE Hiroshi 京都大学, 医学研究科, 講師 (60362498)
• Project Period (FY): 2009 – 2011
• Keywords: 炎症性腸疾患 / サイトメガロウイルス / マクロファージ / サイトカイン

Research Abstract

Analysis of function of macrophages infected with cytomegalovirus(CMV). Macrophages, in which CMV was reactivated, strongly produced more pro-inflammatory cytokines in comparison with macrophages with no CMV reactivation. TGF-βdid not inhibit pro-inflammatory cytokine production from macrophages with CMV reactivation because Smad signal transduction was blocked in those cells.(2)Elucidation of mechanism of CMV infection in intestine of IBD. Gene expressions of PDGFR, etc., which could be entry site of CMV, were up-regulated in inflamed colonic mucosa in comparison with non-inflamed colonic mucosa. Interestingly, immunohistochemistry study revealed that CMV is mainly infected in mesenchymal cells of intestine.

Research Products

• [Journal Article] Involvement of Mycobacterium avium subspecies para tuberculosis with TNF-αproduction from Macrophage-possible link between MAP and immune response in Crohn's disease-Inflammatory Bowel Disease (2011)
  • Author(s): Nakase H, Tamaki H, Matsuura M, Chiba T, Okazaki K
  • Volume: 17
  • Pages: 140-2
  • DOI: doi:10.1002/ibd.21750.
• [Journal Article] Importance of CXCL16 as a biomarker for granulocytapheresis in patients with Crohn's disease (2011)
  • Author(s): Nakase H, Uza N, Matsuura M, Chiba T
  • Journal Title: Inflamm Bowel Dis Volume: 17 Pages: 2211-2
  • DOI: doi:10.1002/ibd.21657.
• [Journal Article] Potential role of granulocyte/monocyte adsorptive apheresis for ulcerative colitis with concomitant CMV infection (2011)
  • Author(s): Nakase H, Matsuura M, Chiba T
  • Journal Title: Aliment Pharmacol Ther Volume: 33 Pages: 497-8
  • DOI: doi:10.1111/j.1365-2036.2010.04552.
• [Journal Article] Tacrolimus suppresses IL-12/IL-23p40 in Crohn's disease and heals fistulae refractory to anti-TNF-αtherapy (2011)
  • Author(s): Nakase H, Uza N, Matsuura M, Chiba T
  • Journal Title: Aliment Pharmacol Ther Volume: 33 Pages: 979-80
  • DOI: doi:10.1111/j.1365-2036.2011.04587.
• [Journal Article] SR-PSOX/CXCL16 plays a critical role in the progression of colonic inflammation (2011)
  • Author(s): Uza N, Nakase H, Yamamoto S, Yoshino T, Takeda Y, Ueno S, Inoue S, Mikami S, Matsuura M, Shimaoka T, Kume N, Minami M, Yonehara S, Ikeuchi H, Chiba T
  • Journal Title: Gut Volume: 60 Pages: 1494-505
  • DOI: doi:10.1136/gut.2010.221879
• [Journal Article] Effect and Safety of Granulocyte-Monocyte Adsorption Apheresis for UC Patients Positive for Cytomegalovirus in Comparison with Immunosuppressants (2011)
  • Author(s): Yoshino T, Nakase H, Matsuura M, Matsumura K, Honzawa Y, Fukuchi T, Watanabe K, Murano M, Tsujikawa T, Fukunaga K, Matsumoto T, Chiba T
  • Journal Title: Digestion Volume: 84 Pages: 3-9
  • DOI: doi:10.1159/000321911
• [Journal Article] Tacrolimus : rescue therapy or experimental drug for severe ulcerative colitis (2011)
  • Author(s): Nakase H, Yamamoto S, Matsuura M, Chiba T
  • Journal Title: Aliment Pharmacol Ther Volume: 33 Pages: 413-4
  • DOI: doi:10.1111/j.1365-2036.2010.04532.
• [Journal Article] Positive finding of Colonic PCR for CMV-DNA is not false positive but warning for treating patients with UC refractory to immunosuppressive therapies Inflammatory Bowel Disease (2011)
  • Author(s): Nakase H Yoshino T, Matsumura K, Honzawa Y, Yamamoto S, Matsuura M, Chiba T
  • Volume: 17
  • Pages: 13-4
  • DOI: doi:10.1002/ibd.21401
• [Journal Article] TNFαis an important pathogenic factor contributing to reactivation of cytomegalovirus in inflamed mucosa of colon in patients with ulcerative colitis-lesson from clinical experiences-. (2010)
  • Author(s): Nakase H, Chiba T
  • Journal Title: Inflammatory Bowel Disease Volume: 16 Pages: 550-551
  • DOI: doi:10.1002/ibd.21047
• [Journal Article] Immunosuppressive effects of tacrolimus on macrophages ameliorate experimental colitis (2010)
  • Author(s): Yoshino T, Nakase H, Honzawa Y, Matsumura K, Yamamoto S, Takeda Y, Ueno S, Uza N, Masuda S, Inui K, Chiba T
  • Journal Title: Inflammatory Bowel Disease Volume: 16 Pages: 2022-33
  • DOI: doi:10.1002/ibd.21318.
• [Presentation] Characteristics of colonoscopic features in patients with ulcerative colitis concomitant with cytomegalovirus reactivation (2011)
  • Author(s): Matsuura M, Nakase H, Honzawa Y, Yamamoto S, Matsumura K, Uza N, Chiba T
  • Organizer: DDW
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-09
• [Presentation] IL-17 promotes HSP47 expression and intestinal fibrosis in Crohn's disease (2011)
  • Author(s): Honzawa Y, Nakase H, Matsumura K, Yamamoto S, Uza N, Matsuura M, Chiba T
  • Organizer: DDW
  • Place of Presentation: Chicago
  • Year and Date: 2011-05-08
• [Presentation] Serum level of heat shock protein 47 could be a useful marker for intestinal fibrosis in patients with Crohn's disease (2010)
  • Author(s): Honzawa Y, Nakase H, Matsumura K, Yamamoto S, Uza N, Matsuura M, Chiba T
  • Organizer: Gut
  • Place of Presentation: UEGW, Barcelona
  • Year and Date: 2010-10-26
• [Presentation] Measurement of serum diamine oxidase(DAO) activity can be a predictive factor of disease onset of human IBD (2010)
  • Author(s): Honzawa Y, Nakase H, Matsumura K, Yamamoto S, Yoshino T, Takeda Y, Ueno S, Uza N, Chiba T
  • Organizer: DDW
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-05
• [Presentation] Role of Heat shock protein 47 in the pathogenesis of patients with Crohn's disease (2010)
  • Author(s): Honzawa Y, Nakase H, Matsumura K, Yamamoto S, Yoshino T, Takeda Y, Ueno S, Uza N, Chiba T
  • Organizer: DDW
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-04
• [Presentation] Novel immunomodulating effect of tacrolimus : induction of apoptosis on macrophage attenuates immune-mediated colitis (2010)
  • Author(s): Yoshino T, Nakase H, Chiba T
  • Organizer: DDW
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-03
• [Presentation] Role of osteopontin in acute graft-versus-host disease (2010)
  • Author(s): Takeda Y, Nakase H, Honzawa Y, Matsumura K, Yamamoto S, Yoshino T, Uza N, Ueno S, Chiba T
  • Organizer: DDW
  • Place of Presentation: New Orleans
  • Year and Date: 2010-05-02
• [Presentation] Use of tacrolimus in in flammatory bowel disease (2010)
  • Author(s): Nakase H
  • Organizer: The 4th Korea-Japan Inflammatory bowel disease Symposium Japan
  • Year and Date: 2010-01-23
• [Presentation] Suppression of LPS-induced NF-kB and p38MAPK activation by FK506 ameliorates murine colitis (2009)
  • Author(s): Yoshino T, Nakase H, Matsumura K, Yamamoto S, Takeda Y, Ueno S, Uza N, Chiba T
  • Organizer: 14th international congress of mucosal immunology
  • Place of Presentation: Boston
  • Year and Date: 2009-07-05
• [Presentation] Acitvation of Innate immune response by osteopontine prevent onset of spontaneous colitis (2009)
  • Author(s): Ueno S, Nakase H, Chiba T
  • Organizer: DDW
  • Place of Presentation: Chicago
  • Year and Date: 2009-06-02
• [Presentation] Regulation of activate macrophages by FK506 attenuates immune-mediated colitis (2009)
  • Author(s): Yoshino T, Nakase H, Matsumura K, Yamamoto S, Takeda Y, Ueno S, Uza N, Chiba T
  • Organizer: DDW
  • Place of Presentation: Chicago
  • Year and Date: 2009-06-01
• [Presentation] The Critical role of CXC chemokine ligand 16/scavenger receptor in the pathogenesis of inflammatory bowel disease (2009)
  • Author(s): Uza N, Nakase H, Chiba T
  • Organizer: DDW
  • Place of Presentation: Chicago
  • Year and Date: 2009-05-31