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15. P081 Effect of bile acid on lymphocyte migration in the small intestine

Author

Shibuya, N, primary, Higashiyama, M, additional, Nishii, S, additional, Mizoguchi, A, additional, Inaba, K, additional, Sugihara, N, additional, Hanawa, Y, additional, Wada, A, additional, Horiuchi, K, additional, Furuhashi, H, additional, Kurihara, C, additional, Hozumi, H, additional, Okada, Y, additional, Watanabe, C, additional, Komoto, S, additional, Tomita, K, additional, Nagao, S, additional, Saruta, M, additional, and Hokari, R, additional

Published
2019
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17. Free cholesterol accumulation in liver sinusoidal endothelial cells exacerbates acetaminophen hepatotoxicity in mice

Author

Teratani, T., primary, Tomita, K., additional, Suzuki, T., additional, Furuhashi, H., additional, Irie, R., additional, Hida, S., additional, Okada, Y., additional, Kurihara, C., additional, Ebinuma, H., additional, Nakamoto, N., additional, Saito, H., additional, Hibi, T., additional, Miura, S., additional, Hokari, R., additional, and Kanai, T., additional

Published
2017
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18. P599 ACYL-COENZYME A:CHOLESTEROL ACYLTRANSFERASE 1 DEFICIENCY EXAGGERATES LIVER FIBROSIS THROUGH ENHANCED FREE CHOLESTEROL ACCUMULATION IN HEPATIC STELLATE CELLS

Author

Tomita, K., primary, Teratani, T., additional, Suzuki, T., additional, Shimizu, M., additional, Sato, H., additional, Narimatsu, K., additional, Usui, S., additional, Kimura, A., additional, Nishiyama, K., additional, Maejima, T., additional, Okada, Y., additional, Kurihara, C., additional, Shimamura, K., additional, Ebinuma, H., additional, Saito, H., additional, Yokoyama, H., additional, Watanabe, C., additional, Komoto, S., additional, Nagao, S., additional, Sugiyama, K., additional, Aozasa, S., additional, Hatsuse, K., additional, Yamamoto, J., additional, Hibi, T., additional, Miura, S., additional, Hokari, R., additional, and Kanai, T., additional

Published
2014
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19. 1302 THE CHARACTERISTIC MECHANISMS OF FREE CHOLESTEROL ACCUMULATION IN HEPATIC STELLATE CELLS AGGRAVATE LIVER FIBROSIS IN NONALCOHOLIC STEATOHEPATITIS IN MICE

Author

Tomita, K., primary, Teratani, T., additional, Suzuki, T., additional, Shimizu, M., additional, Sato, H., additional, Okada, Y., additional, Kurihara, C., additional, Yokoyama, H., additional, Irie, R., additional, Ebinuma, H., additional, Saito, H., additional, Watanabe, C., additional, Komoto, S., additional, Hokari, R., additional, Kawaguchi, A., additional, Nagao, S., additional, Sugiyama, K., additional, Kanai, T., additional, Hibi, T., additional, and Miura, S., additional

Published
2013
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20. 1265 P53/P66SHC SIGNALING PATHWAY PLAYS A ROLE IN NONALCOHOLIC STEATOHEPATITIS PROGRESSION IN HUMAN AND MICE

Author

Tomka, K., primary, Teratani, T., additional, Suzuki, T., additional, Yokoyama, H., additional, Shimamura, K., additional, Nishiyama, K., additional, Okada, Y., additional, Kurihara, C., additional, Ebinuma, H., additional, Saito, H., additional, Hokari, R., additional, Sugiyama, K., additional, Hatsuse, K., additional, Yamamoto, J., additional, Kanai, T., additional, Hibi, T., additional, and Miura, S., additional

Published
2012
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30. Enhanced lymphocyte interaction in postcapillary venules of Peyer's patches during fat absorption in rats

Author

Tsuzuki, Y, primary, Miura, S, additional, Kurose, I, additional, Suematsu, M, additional, Higuchi, H, additional, Shigematsu, T, additional, Kimura, H, additional, Serizawa, H, additional, Hokari, R, additional, Akiba, Y, additional, Yagita, H, additional, Okumura, K, additional, Tso, P, additional, Granger, DN, additional, and Ishii, H, additional

Published
1997
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34. Propionibacterium freudenreichii component 1 .4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing.

Author

Okada, Y., Tsuzuki, Y., Miyazaki, J., Matsuzaki, K., Hokari, R., Komoto, S., Kato, S., Kawaguchi, A., Nagao, S., Itoh, K., Watanabe, I., and Miura, S.

Subjects
PROPIONIBACTERIUM, COLITIS, LYMPHOCYTES, SODIUM sulfate, CYTOKINES, MESSENGER RNA
Abstract

Background and aim: 1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic; however, its in vivo effect on intestinal inflammation remains unknown. The aim of this study was to determine whether oral administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced colitis and to determine the possible underlying mechanisms. Method: Colitis was induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0 mg/ kg) was given in drinking water prior to (preventive study) or after (therapeutic study) DSS administration. Colonic damage was histologically scored, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression and β7 positive cell infiltration were determined by immunohistochemistry, mRNA levels of proinflammatory cytokines (interleukin (IL)-1β, IL-6 and tumour necrosis factor α (TNF-α)) were determined by quantitative real time polymerase chain reaction. In addition, bacterial flora in the caecum, concentrations of short chain acids, and luminal pH were examined. Results: DHNA improved survival rate and histological damage score in mice administered DSS in both the preventive and therapeutic studies. DHNA significantly attenuated the enhanced expression of MAdCAM-1, the increased 137 positive cell number, and the increased mRNA levels of IL-1β, IL-6, and TNF-α in DSS treated colon. In addition, the decreased number of Lactobacillus and Enterabacteriaceae induced by DSS was recovered by DHNA. Preventive effects on decrease in butyrate concentration and decrease in pH level in mice administered DSS were also observed in the DHNA preventive study. Conclusion: DHNA, a novel type of prebiotic, attenuates colonic inflammation not only by balancing intestinal bacterial flora but also by suppressing lymphocyte infiltration through reduction of MAdCAM-1. [ABSTRACT FROM AUTHOR]

Published
2006
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35. Differential modulation in the functions of intestinal dendritic cells by long- and medium-chain fatty acids.

Author

Ysuzuki Y, Miyazaki J, Matsuzaki K, Okada Y, Hokari R, Kawaguchi A, Nagao S, Itoh K, Miura S, Tsuzuki, Yoshikazu, Miyazaki, Jyunichi, Matsuzaki, Koji, Okada, Yoshikiyo, Hokari, Ryota, Kawaguchi, Atsushi, Nagao, Shigeaki, Itoh, Kazuro, and Miura, Soichiro

Abstract

Background: Although dendritic cells (DCs) play significant roles in intestinal immune responses, little is known regarding the direct effects of luminal foods on DC functions in the intestinal mucosa. In this study, we examined the effects of fatty acids (FAs) with various chain length on the phagocytic function, antigen presentation, and chemotaxis of intestinal DCs.Methods: DCs obtained from the thoracic duct lymph of mesenteric lymphadenectomized rats were cultured with long [arachidonic acid (AA) or oleic acid] or medium (octanoic acid) chain FAs with interleukin-4 and granulocyte macrophage-colony stimulating factor. Tumor necrosis factor-alpha was added in the maturation group. Phagocytic function was examined by the intake of fluorescent microbeads. The expression of cell surface molecules was determined by immunocytochemistry or fluorescence-activated cell sorting (FACS). Antigen presentation ability was evaluated by coincubating keyhole limpet hemocyanin (KLH)-sensitized spleen lymphocytes and KLH-pulsed DCs. Migratory ability of DCs toward the chemokines CC chemokine ligand (CCL) 20 and CCL21 was also assessed.Results: There was a maturation-induced decrease in phagocytic function, and an increased expression of major histocompatibility complex (MHC) class II molecules. Exposure of DCs to both long- and medium-chain FAs maintained phagocytic ability. The expression of MHC class II molecules was significantly suppressed only by long-chain FAs. The expression of costimulatory factors was suppressed only by AA. Long- but not medium-chain FAs suppressed the antigen presentation ability of DCs induced by maturation. Chemotactic ability of mature DCs toward CCL21 was abrogated only by long-chain FAs.Conclusions: The data suggest that intraluminal exposure to long- and medium-chain FAs may differentially modulate the immune functions of intestinal DCs. [ABSTRACT FROM AUTHOR]

Published
2006

36. In vivodemonstration of T lymphocyte migration and amelioration of ileitis in intestinal mucosa of SAMP1/Yit mice by the inhibition of MAdCAM-1.

Author

Matsuzaki, K., Tsuzuki, Y., Matsunaga, H., Inoue, T., Miyazaki, J., Hokari, R., Okada, Y., Kawaguchi, A., Nagao, S., Itoh, K., Matsumoto, S., and Miura, S.

Subjects
T cells, ILEUM diseases, INTESTINAL mucosa, IMMUNOHISTOCHEMISTRY, INTEGRINS, IMMUNOGLOBULINS
Abstract

The aetiology of Crohn's disease (CD) remains unknown. Since SAMP1/Yit mice have been reported to develop CD-like spontaneous enteric inflammation, such mice have been studied as an animal model of CD. In this study, using this model we examined T lymphocyte migration in microvessels of intestinal mucosain vivoand the expression of adhesion molecules by immunohistochemistry. Fluorescence-labelled T lymphocytes isolated from AKR/J (control) mice were injected into the tail veins of recipient mice, and T lymphocyte migration in the postcapillary venules of Peyer's patches, submucosal microvessels, and villus capillaries of the terminal ileum was monitored using an intravital microscope. Adhesion of T lymphocytes was significantly increased in 35 week old SAMP1/Yit mice compared with that in AKR/J or 15 week old SAMP1/Yit mice. Immunohistochemical study showed increased infiltration of CD4, CD8 andβ7-integrin-positive cells and increased expression of MAdCAM-1 and VCAM-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against MAdCAM-1 and VCAM-1 significantly inhibited adhesion of T lymphocytes to microvessels of the terminal ileum, and anti-MAdCAM-1 antibody showed stronger suppressive effect than the anti-VCAM-1 antibody. Periodical administration of anti-MAdCAM-1 antibody twice a week for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice, but submucosal hypertrophy was not significantly suppressed. Anti-VCAM-1 antibody treatment failed to show significant resolution of ileitis. In addition, anti-MAdCAM-1 antibody treatment also attenuated established ileitis. The results demonstrate that, although MAdCAM-1 and VCAM-1 play an important role in T lymphocyte–endothelial cell interactions in SAMP1/Yit mice, MAdCAM-1 may be a more appropriate target for therapeutic modulation of chronic ileitis. [ABSTRACT FROM AUTHOR]

Published
2005
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38. Newly designed soft prelooped cap for endoscopic mucosal resection of gastric lesions

Author

Matsuzaki, K., Nagao, S., Kawaguchi, A., Miyazaki, J., Yoshida, Y., Kitagawa, Y., Nakajima, H., Kato, S., Hokari, R., Tsuzuki, Y., Itoh, K., Niwa, H., and Miura, S.

Abstract

Background Endoscopic mucosal resection with a capfitted panendoscope is a useful, effective, and safe technique. The effectiveness and safety of a newly designed larger but softer cap was compared in this study with the conventional hard cap. The soft cap has a significantly larger diameter (18 mm) compared with that of the hard cap (16.5 mm). Methods: Eighty-three patients who underwent mucosal resection of gastric lesions were included in analysis. The diameter, resection specimen depth, and the rate of en bloc resection were compared. The operability of the endoscope with the cap attached, patient tolerance, and safety of the procedure were analyzed. Results: Mean diameter (+/-SEM) of specimens resected with the soft cap was larger: 22.1 (+/-0.7) versus 15.8 (+/-0.3) mm (p<0.001). The specimen was also thicker: 1.54 (+/-0.10) versus 1.08 (+/-0.11) mm (p<0.001). Use of the soft cap led to higher rate of en bloc resection: 66.7% versus 43.2% (p<0.05). The operability of the endoscope with the larger, softer cap attached was similar to that when the hard cap was used. Both caps were equally safe. Conclusion: The soft cap is safe and useful for mucosal resection of larger gastric lesions. Its use increases the rate of en bloc resection.

Published
2003
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39. In situ demonstration of intraepithelial lymphocyte adhesion to villus microvessels of the small intestine

Author

Hachimura, S., Koseki, S., Kaminogawa, S., Miura, S., Ishii, H., Fujimori, H., Hokari, R., Komoto, S., Hara, Y., Ogino, T., Nagata, H., and Goto, M.

Abstract

The recirculation of lymphocytes through the intestinal mucosa is important for specific immune defense, but the origin and differentiation of intraepithelial lymphocytes (IEL) are not fully understood. The present study therefore used intravital microscopy to investigate the migration of IEL to the villus mucosa and Peyer's patches of the small intestine. IEL were separated from inverted murine small intestine and mesenteric lymph node (MLN) T cells were also isolated. The adhesion of fluorescence-labeled lymphocytes to postcapillary venules (PCV) of Peyer's patches and arcade microvessels of small intestinal villi was observed after injection. In some experiments, the effect of antibodies against adhesion molecules on cell kinetics were investigated. IEL time-dependently accumulated in villus microvessels of the small intestine, whereas few MLN cells did. Few IEL adhered to the PCV of Peyer's patches. IEL were shown to express αEβ7-integrin but not L-selectin. The accumulation of IEL in villus archade was significantly inhibited by antibody against β7-integrin or mucosal addressin cell adhesion molecules (MAdCAM)-1, but not by αE-integrin. The combined blocking of β7-integrin and MAdCAM-1 further attenuated the sticking of IEL in this area, although it did not entirely block the IEL adherence. The adherence of CD4+ or TCRαβ IEL to villus microvessels was significantly greater than that of CD4- or TCRγδ IEL. It was demonstrated in situ for the first time that IEL adhered selectively to the villus microvessels of the small intestine partly via β7 and MAdCAM-1.

Published
2001

40. In situ demonstration of intraepithelial lymphocyte adhesion to villus microvessels of the small intestine.

Author

Koseki, S, Miura, S, Fujimori, H, Hokari, R, Komoto, S, Hara, Y, Ogino, T, Nagata, H, Goto, M, Hachimura, S, Kaminogawa, S, and Ishii, H

Abstract

The recirculation of lymphocytes through the intestinal mucosa is important for specific immune defense, but the origin and differentiation of intraepithelial lymphocytes (IEL) are not fully understood. The present study therefore used intravital microscopy to investigate the migration of IEL to the villus mucosa and Peyer's patches of the small intestine. IEL were separated from inverted murine small intestine and mesenteric lymph node (MLN) T cells were also isolated. The adhesion of fluorescence-labeled lymphocytes to postcapillary venules (PCV) of Peyer's patches and arcade microvessels of small intestinal villi was observed after injection. In some experiments, the effect of antibodies against adhesion molecules on cell kinetics were investigated. IEL time-dependently accumulated in villus microvessels of the small intestine, whereas few MLN cells did. Few IEL adhered to the PCV of Peyer's patches. IEL were shown to express alpha(E)beta(7)-integrin but not L-selectin. The accumulation of IEL in villus archade was significantly inhibited by antibody against beta(7)-integrin or mucosal addressin cell adhesion molecules (MAdCAM)-1, but not by alpha(E)-integrin. The combined blocking of beta(7)-integrin and MAdCAM-1 further attenuated the sticking of IEL in this area, although it did not entirely block the IEL adherence. The adherence of CD4(+) or TCRalphabeta IEL to villus microvessels was significantly greater than that of CD4(-) or TCRgammadelta IEL. It was demonstrated in situ for the first time that IEL adhered selectively to the villus microvessels of the small intestine partly via beta(7) and MAdCAM-1.

Published
2001
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43. Nitric oxide modulates T-lymphocyte migration in Peyer's patches and villous submucosa of rat small intestine

Author

Hokari^*, R., Miura^@?, S., Fujimori^*, H., Tsuzuki^*, Y., Shigematsu^*, T., Higuchi^*, H., Kimura^*, H., Kurose^*, I., Serizawa^*, H., Suematsu^&, M., Yagita^@?, H., Granger^@?, D., and Ishii^*, H.

Abstract

Background & Aims: Although nitric oxide (NO) is known to influence the recruitment of neutrophils in inflamed tissue, its role in lymphocyte-endothelial cell interactions remains poorly understood. The objectives of this study were to assess the effects of NO synthesis inhibition on T-lymphocyte migration in microvessels of rat small intestine and to define the role of adhesion molecules in this process. Methods: T lymphocytes collected from rat intestinal lymph were labeled with carboxyfluorescein diacetate succinimidyl ester and injected into the jugular vein of recipient rats. The migration of T lymphocytes into normal and N^G-nitro-L-arginine methyl ester (L-NAME)-treated intestinal microvessels was monitored by using an intravital microscope. Results:L-NAME significantly increased rolling and adherence of lymphocytes in postcapillary venules of Peyer's patches and submucosal venules without significantly decreasing red blood cell velocity. The subsequent appearance of lymphocytes in the initial lymphatics was also accelerated by L-NAME. Anti-@a4-integrin antibody markedly inhibited the L-NAME-induced lymphocyte-endothelial cell interaction. Anti-P-selectin monoclonal antibody also significantly attenuated these adhesive interactions in both vascular regions. Conclusions: These data suggest that NO is an important modulator of lymphocyte migration in Peyer's patches and in nonlymphoid regions of the intestine. GASTROENTEROLOGY 1998;115:618-627

Published
1998
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46. Human intestinal spirochetosis accompanied by human immunodeficiency virus infection: A Case report

Author

Masaaki Higashiyama, Ogata S, Adachi Y, Nishiyama J, Ohara I, Okamura M, Matsuzaki K, Okusa Y, Sato K, Hokari R, and Miura S

Subjects
Intestines, Male, Intestinal Diseases, Brachyspira, human intestinal spirochetosis, human immunodeficiency virus, entameba, syphilis, Humans, HIV Infections, Spirochaetales Infections, Middle Aged
Abstract

We present a middle-aged, heterosexual Japanese man with mixed infections including human intestinal spirochetosis, which led us to the detection of human immunodeficiency virus (HIV) infection. The patient had syphilis without related physical or neurological findings. An examination for the serum antibody for HIV performed 9 years previously was negative. In a complete medical checkup at the present time, human intestinal spirochetosis and unspecified entamebic cysts were suggested by histological examination of colonic biopsy material and parasitic examination of the intestinal fluid, respectively. Moreover, a serological test for the antibody for HIV was positive. In specimens obtained by colonoscopy, Brachyspira aalborgi was diagnosed by ultrastructural study and the polymerase chain reaction method for bacterial 16S ribosomal deoxyribonucleic acid. Although HIV infection remains at low prevalence in Japan, we recommend examination for HIV infection in patients with human intestinal spirochetosis, especially when other co-infections are apparent.

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