研究者詳細 - 佐藤　俊朗

論文 - 佐藤　俊朗

分割表示 96 件中 81 - 96 件目／全件表示 >>

Nonpathogenic Escherichia coli strain Nissle 1917 prevents murine acute and chronic colitis

Kamada Nobuhiko, Inoue Nagamu, Hisamatsu Tadakazu, Okamoto Susumu, Matsuoka Katsuyoshi, Sato Toshiro, Chinen Hiroshi, Hong Kyong Su, Yamada Takaya, Suzuki Yumiko, Suzuki Tatsuo, Watanabe Noriaki, Tsuchimoto Kanji, Hibi Toshifumi

Inflammatory Bowel Diseases 11 （ 5 ） 455 - 463 2005年05月

ISSN 1078-0998

Background: Nonpathogenic Escherichia coli strain Nissle1917 has been used as a probiotics in human inflammatory bowel disease; however, there are few reports examining its therapeutic effect on animal colitis models, and its therapeutic mechanisms remain unknown. The aim of this study was to elucidate the therapeutic effect and mechanism of Nissle1917 using murine acute and chronic colitis models. Methods: Two models were used. (1) Acute model: colitis was induced by administration of 1.3% dextran sodium sulfate for 7 days. Nissle1917 or phosphate-buffered saline were orally administered for 10 days. Mice were killed at day 10, and the colonic lesions were assessed macro- and microscopically. (2) Chronic model: IL-10^-/- mice were treated with Nissle1917 or phosphate-buffered saline for 8 weeks. After 8 weeks of treatment, mice were killed to assess the colonic lesions macro- and microscopically. In the acute dextran sodium sulfate colitis model, viable, heat-killed, or genomic DNA of Nissle1917 was orally administered for 10 days, and the therapeutic effect was assessed. Results: In the acute model, Nissle1917 ameliorated body weight loss, disease activity index, and macro- and microscopic damage. In the chronic model, it also suppressed the mucosal inflammatory findings and histologic damages. Moreover, heat-killed Nissle1917 or its genomic DNA alone also ameliorated the acute DSS colitis and viable bacteria macro- and microscopically. Conclusions: Nonpathogenic E. coli strain Nissle1917 prevents both acute and chronic colitis, and its anti-inflammatory effect is exhibited not only by viable bacteria but also by heat-killed bacteria or its DNA.

Access to Document (DOI)

T-bet upregulation and subsequent interleukin 12 stimulation are essential for induction or Th1 mediated immunopathology in Crohn's disease

Matsuoka K., Inoue N., Sato T., Okamoto S., Hisamatsu T., Kishi Y., Sakuraba A., Hitotsumatsu O., Ogata H., Koganei K., Fukushima T., Kanai T., Watanabe M., Ishii H., Hibi T.

Gut 53 （ 9 ） 1303 - 1308 2004年09月

ISSN 0017-5749

Background and aims: Many lines of evidence suggest that T helper cell type 1 (Th1) immune responses predominate in Crohn's disease (CD). Recently, a novel transcription factor T-box expressed in T cells (T-bet) has been reported as the master regulator of Th1 development. This study was designed to investigate the role of T-bet and proinflammatory cytokines in Th1 mediated immunopathology in CD. Materials: CD4+ lamina propria mononuclear cells (LPMCs) were isolated from surgically resected specimens (CD, n = 10; ulcerative colitis (UC), n = 10; normal controls (NL), n = 5). Methods: (1) T-bet expression of CD4+ LPMCs was examined by quantitative real time polymerase chain reaction and western blotting. (2) T-bet expression of LPMCs stimulated by interleukin (IL)-12/IL-18 was analysed by western blotting. (3) Interferon γ (IFN-γ) production and T-bet expression of CD4+ peripheral blood mononuclear cells (PBMCs) were examined with or without stimulation by anti-CD3/CD28 monoclonal antibodies and/or IL-12. Results: (1) T-bet expression of CD4+ LPMCs was increased in CD compared with UC and NL. (2) Synergistically, augmentation of IFN-γ production by IL-12/IL-18 was independent of T-bet expression in LPMCs. (3) T-bet was induced by T cell receptor stimulation in CD4+ PBMCs. T-bet induction correlated with IFN-γ production and with augmentation of surface expressed IL-12 receptor β2. Conclusions: T-bet induction by antigenic stimulation and subsequent stimulation by macrophage derived IL-12/IL-18 are important for establishing Th1 mediated immunopathology in CD.

Access to Document (DOI)

Human intestinal epithelial cell-derived interleukin (IL)-18, along with IL2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes

Okazawa A., Kanai T., Nakamaru K., Sato T., Inoue N., Ogata H., Iwao Y., Ikeda M., Kawamura T., Makita S., Uraushihara K., Okamoto R., Yamazaki M., Kurimoto M., Ishii H., Watanabe M., Hibi T.

Clinical and Experimental Immunology 136 （ 2 ） 269 - 276 2004年05月

ISSN 0009-9104

Intestinal epithelial cell (IEC)-derived cytokines, such as stem cell factor (SCF), interleukin (IL)-7 and IL-15 are known to be required for the development of intestinal intraepithelial lymphocytes (IELs). A newly described cytokine, IL-18, has also been shown to be produced by intestinal epithelial cells. To demonstrate the functional effects of IL-18 on human IELs, we assessed IL-18/IL-18 receptor expression in IEC/IEL and proliferation following stimulation of intestinal IELs by IL-18. IL-18 transcripts were detected both in freshly isolated human colonie epithelial cells and in various colonie epithelial cell lines. IL-18 protein was also detected by ELISA and flow cytometric analysis using antihuman IL-18-specific monoclonal antibody (MoAb). Furthermore, IELs constitutively expressed the IL-18 receptor in addition to the IL-2 and IL-7 receptors. More importantly, IL-18 augmented significant proliferative responses of IEL in combination with IL-2, IL-7 and IL-15 both in the presence and in absence of anti-CD3 MoAb. These results suggest that IL-18 might play a crucial role in the proliferation and maintenance of intestinal IELs.

Access to Document (DOI)

Hyperexpression of Inducible Costimulator and Its Contribution on Lamina Propria T Cells in Inflammatory Bowel Disease

Sato Toshiro, Kanai Takanori, Watanabe Mamoru, Sakuraba Atsushi, Okamoto Susumu, Nakai Takaaki, Okazawa Akira, Inoue Nagamu, Totsuka Teruji, Yamazaki Motomi, Kroczek Richard A., Fukushima Tsuneo, Ishii Hiromasa, Hibi Toshifumi

Gastroenterology 126 （ 3 ） 829 - 839 2004年03月

ISSN 0016-5085

Background & Aims: To investigate the role of inducible costimulator (ICOS), a new member of the CD28 family involved in regulation of T-cell activation and chronic intestinal inflammation, we assessed its expression and functional role in patients with inflammatory bowel disease (IBD). Methods: Expression of ICOS, CD28, and cytotoxic T-lymphocyte antigen (CTLA) 4 on intestinal lamina propria mononuclear cells (LPMC) from patients with ulcerative colitis (UC), Crohn's disease (CD), and normal controls was determined using flow cytometry and immunohistochemistry. Expressions of the ICOS ligand, B7h, on lamina propria B cells, macrophages, and epithelial cells (EC) in the intestinal mucosa were also determined using flow cytometry. The functional costimulatory effect of ICOS on LPMC was assessed by the proliferative response and cytokine production. Results: CD4⁺ LPMC expressing ICOS was significantly increased in the inflamed mucosa of IBD patients but not in inflammatory or normal controls. B7h was also significantly up-regulated on B cells, macrophages, and EC in inflamed mucosa of IBD patients. Proliferative responses of anti-CD3/ICOS costimulation were significantly higher compared with those of anti-CD3 monoclonal antibody (mAb) alone. Anti-CD3/ICOS-stimulated-LPMC from UC secreted significantly increased amounts of interleukin (IL)-5 among the 3 groups. In contrast, anti-CD3/ICOS-stimulated-LPMC from CD secreted significantly increased amounts of interferon (IFN)-γ in the presence of IL-12. Conclusions: Highly expressed ICOS in activated CD4⁺ LPMC of IBD patients contributes to the dysregulated immune responses in IBD. Because ICOS hyperexpression was limited to inflammatory sites in IBD patients, ICOS would be a feasible therapeutic target for the treatment of IBD.

Access to Document (DOI)

Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice

Takagi H., Kanai T., Okazawa A., Kishi Y., Sato T., Takaishi H., Inoue N., Ogata H., Iwao Y., Hoshino K., Takeda K., Akira S., Watanabe M., Ishii H., Hibi Toshifumi

Scandinavian Journal of Gastroenterology 38 （ 8 ） 837 - 844 2003年08月

ISSN 0036-5521

Background: Interleukin (IL)-12 and IL-18 are major interferon (IFN)-γ-inducing factors that collaborate with each other. The present study was conducted to determine the distinct roles of IL-12 and IL-18 in the development of dextran sulphate sodium (DSS) colitis in mice. Methods: Colitis was induced in IL-12p35^-/-, IL-18^-/-, IL-18 receptor ^-/- and control mice with DSS. Clinical and histopathological analysis was conducted using survival rate, weight loss score, diarrhoea score, bloody stool score and histological score. In addition, cytokine production by lamina propria mononuclear cells (LPMCs) was examined using the specific enzyme-linked immunoassay. Results: IL-12p35^-/- mice developed only a mild disease associated with no lethality and few histopathological abnormalities. In contrast, IL-18^-/- and IL-18R^-/- mice developed more severe colitis associated with high lethality and more histopathological abnormalities compared with control mice. LPMCs from DSS-fed IL-18^-/- mice produced significantly higher amounts of IFN-γ, while LPMCs from DSS-fed IL-12^-/- mice produced lower amounts of IFN-γ and tumour necrosis factor (TNF)-α compared with control mice. Conclusion: These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis.

Access to Document (DOI)

下部消化管疾患

佐藤俊朗，日比紀文

内科 90 （ 6 ） 1024-1027 2002年12月

研究論文（学術雑誌）, 共著

炎症性腸疾患

佐藤俊朗，日比紀文

Annual review 消化器 2002 239-243 2002年

研究論文（学術雑誌）, 共著

The citrus flavonoid, nobiletin, inhibits peritoneal dissemination of human gastric carcinoma in SCID mice

Minagawa Akiko, Otani Yoshihide, Kubota Teturo, Wada Norihito, Furukawa Toshiharu, Kumai Koichirou, Kameyama, Kaori, Okada Yasunori, Fujii Masato, Yano Masamichi, Sato Takashi, Ito Akira, Kitajima Masaki

Japanese Journal of Cancer Research 92 （ 12 ） 1322-1328 2001年12月

研究論文（学術雑誌）, 共著

HLA class-I-restricted and colon-specific cytotoxic T cells from lamina propria lymphocytes of patients with ulcerative colitis

Sunagawa Takesh, Yonamine Yoshimasa, Kinjo Fukunori, Watanabe Mamoru, Hibi Toshifumi, Saito Atsushi

Journal of Clinical Immunology 21 （ 6 ） 381-389 2001年11月

研究論文（学術雑誌）, 共著

Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn's disease

Kanai Takanori, Watanabe Mamoru, Okazawa Akira, Sato Toshiro, Yamazaki Motomi, Okamoto Susumu, Ishii Hiromasa, Totsuka Teruji, Iiyama Ryoichi, Okamoto Ryuichi, Ikeda Masao, Kurimoto Masashi, Takeda Kiyoshi, Akira Shizuo, Hibi Toshifumi

Gastroenterology 121 （ 4 ） 875 - 888 2001年10月

研究論文（学術雑誌）, 共著, ISSN 0016-5085

<p>Background & Aims: Crohn's disease (CD) is associated with an increased number of infiltrating macrophages, which release a variety of proinflammatory cytokines. Interleukin (IL)-18 has been implicated in the modulation of mucosal CD4 ⁺ T cells towards Th1 responses, which are implicated in the pathogenesis of CD. Here we assess the role of macrophages and of IL-18 in the murine model of intestinal inflammation that mimics the immunologic characteristics of human CD. Methods: Colitis was induced in C57BL/6 mice immunized with 2,4,6-trinitrobenzene sulfonic acid (TNBS) followed by rectal administration of TNBS in ethanol. Mice were treated with either an antibody directed against macrophages conjugated to the ribosome-inactivating protein saporin (anti-Mac-1-saporin) or with a neutralizing antibody against IL-18. In addition, we assessed whether an identical TNBS immunization/challenge protocol could induce colitis in IL-18 ^-/- mice. Results: The colonic mucosa of TNBS-treated mice was marked by infiltration of Mac-1-positive macrophages and up-regulation of IL-18. The administration of the anti-Mac-1-saporin antibody or the neutralizing anti-IL-18 antibody resulted in a dramatic attenuation of mucosal inflammation in this model. In addition, TNBS was unable to induce significant colitis in the IL-18 ^-/- mice. Conclusions: Our data underscore the pivotal role of macrophages, and the macrophage-derived IL-18, in the establishment of TNBS-induced colitis in mice. Our results highlight the potential use of therapy directed against IL-18 in the treatment of patients with CD.</p>

Restricted VH Gene usage in lamina propria B Cells producing anticolon antibody from patients with ulcerative colitis

Inoue Nagamu, Watanabe Mamoru, Sato Toshirou, Okazawa Akira, Yamazaki Motomi, Kanai Takanori, Ogata Haruhiko, Iwao Yasushi, Ishii Hiromasa，Hibi Toshifumi

Gastroenterology　 121 （ 1 ） 15-23 2001年07月

研究論文（学術雑誌）, 共著

内視鏡的に摘出しえた回腸アニサキス症の1例

佐藤俊朗，今枝博之，緒方晴彦，岩男泰，細田泰雄，長沼誠，江崎俊彦，中澤敦，井上詠，日比紀文，石井裕正，向井万起男

Progress of Digestive Endoscopy 58 112-113 2001年06月

研究論文（学術雑誌）, 共著

Interleukin-18 and Crohn's disease

Kanai Takanori, Watanabe Mamoru, Okazawa Akira, Sato Toshiro, Hibi Toshifumi

Digestion 63 （ suppl. 1 ） 37 - 42 2001年01月

研究論文（学術雑誌）, 共著, ISSN 0012-2823

The etiology and pathogenesis of inflammatory bowel disease remains an area under intense investigation. Crohn's disease (CD) is characterized by a marked accumulation of activated Th1 type CD4+ T cells and macrophages in inflamed intestinal mucosa. IL-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4+ T cells by inducing interferon-γ. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes in human CD and murine CD model.</p>

Access to Document (DOI)

Restricted V_H gene usage in lamina propria B cells producing anticolon antibody from patients with ulcerative colitis

Inoue Nagamu, Watanabe Mamoru, Sato Toshiro, Okazawa Akira, Yamazaki Motomi, Kanai Takanori, Ogata Haruhiko, Iwao Yasushi, Ishii Hiromasa, Hibi Toshifumi

Gastroenterology 121 （ 1 ） 15 - 23 2001年

ISSN 0016-5085

Background & Aims: Autoimmune responses against colonic epithelium may play a role in the development of colonic inflammation associated with ulcerative colitis (UC). In this study, we established and characterized B-cell lines and clones that produced anticolon antibody from inflamed colonic mucosa of UC subjects. Methods: B-cell lines were generated through Epstein-Barr virus transformation of lamina propria lymphocytes (LPLs) from colonic mucosa and peripheral blood lymphocytes, and these lines were screened for the production of anticolon antibodies. B-cell lines were then cloned by limiting dilution culture, and messenger RNA expression of immunoglobulin heavy-chain variable region (V_H) was assessed. Results: V_H gene families used in B-cell lines established from LPLs of normal controls were diverse, and B-cell lines from UC LPLs expressed a restricted V_H3 family usage. All 15 clones from UC used a restricted V_H3 gene family, whereas diverse V_H gene families were used by 24 clones from normal controls. The analysis of nucleotide sequences indicated that these clones were derived from various germline gene segments. Conclusions: The restricted V_H gene usage in anticolon autoantibodies producing B-cell clones suggests that a particular antigenic stimulus contributes to the pathogenesis of UC.

クローン病におけるIL-18の関与

日比紀文，金井隆典，渡辺守，岡沢啓，佐藤俊朗

日本臨床免疫学会会誌 23 （ 6 ） 607-610 2000年12月

研究論文（その他学術会議資料等）, 共著

実験動物モデル

佐藤俊朗，渡辺守，日比紀文

消化器病セミナー 77 111-122 1999年12月

研究論文（学術雑誌）, 共著

　前のページ - 次のページ　

佐藤 俊朗

論文 - 佐藤 俊朗

佐藤　俊朗

論文 - 佐藤　俊朗