T Ohkawara

Publications (5)11.38 Total impact

• Article: DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis.

  T Ohkawara, Y Koyama, S Onodera, H Takeda, M Kato, M Asaka, J Nishihira
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  ABSTRACT: Previous studies have shown that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibody reduces intestinal inflammation in mice. In this study we tested whether or not anti-MIF autoantibody induced by DNA vaccine targeting MIF protects mice against experimental colitis. Mice were administered a MIF-deoxyribonucleic acid (DNA) vaccine by introducing oligonucleotides encoding helper T epitope into the cDNA sequence of murine MIF by in vivo electroporation. Preventive effects of this method against dextran sulphate sodium-induced (DSS) colitis were evaluated. Mice administered with MIF-DNA vaccine raised values of autoantibody significantly. The clinical and histological findings of colitis induced by 3·0% DSS solution were ameliorated significantly in mice treated with MIF-DNA vaccine compared with saline or pCAGGS-treated mice given DSS. Myeloperoxidase activity, infiltration of F4/80-positive staining cells and the levels of proinflammatory cytokines were suppressed in the colon of MIF-DNA vaccine treated mice compared with saline or pCAGGS-treated mice exposed to DSS. Our results suggest that immunization with helper T epitope DNA-vaccine targeting MIF may be a useful approach for the treatment of colitis including inflammatory bowel diseases.
  Clinical & Experimental Immunology 11/2010; 163(1):113-22. · 3.36 Impact Factor
• Source

  Available from: umich.edu

  Article: Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation.

  T Toubai, Y Shono, J Nishihira, M Ibata, J Suigita, N Kato, T Ohkawara, S Tone, K P Lowler, S Ota, J Tanaka, M Asaka, P Reddy, M Imamura
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  ABSTRACT: Macrophage migration inhibitory factor (MIF) may play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), as MIF plays an important role to regulate the production of tumor necrosis factor-alpha (TNF-alpha), one of the inflammatory cytokines which induces and exacerbates aGVHD. We examined the association between serum MIF levels and aGVHD vs. chronic GVHD (cGVHD) in allo-SCT patients in this study. We found a significant increase in the peak serum MIF (14.46 ng +/- 1.47 ng/ml) at onset in patients that developed aGVHD (n = 23, P = 0.009). We also found that mean serum MIF levels in patients who developed extensive type cGVHD within 6 months (12.58 +/- 2.18 ng/ml, n = 13) were significantly higher than MIF levels before allo-HSCT (7.86 +/- 1.17 ng/ml, n = 19, P = 0.04). Therefore, we speculated that serum MIF levels increase during the active phase of both aGVHD and cGVHD.
  International journal of laboratory hematology 01/2008; 31(2):161-8. · 1.30 Impact Factor
• Article: Macrophage migration inhibitory factor contributes to the development of acute dextran sulphate sodium-induced colitis in Toll-like receptor 4 knockout mice.

  T Ohkawara, H Takeda, J Nishihira, K Miyashita, M Nihiwaki, Y Ishiguro, K Takeda, S Akira, T Iwanaga, T Sugiyama, M Asaka
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  ABSTRACT: Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharides, plays an important role in the innate immune response. In this study, we investigated the role of TLR4 in the development of experimental colitis with regard to the biological actions of macrophage migration inhibitory factor (MIF) using TLR4 null ((-/-)) mice. TLR4(-/-) mice were given 2% dextran sulphate sodium (DSS) in drinking water to induce colitis, which was clinically and histologically as severe as that seen in wild-type (WT) mice. The level of tumour necrosis factor (TNF)-alpha in colon tissues was increased in WT mice but unchanged in TLR4(-/-) mice. The level of myeloperoxidase (MPO) activity in colon tissues was increased by DSS administration in both TLR4(-/-) and WT mice. The expression of MIF was up-regulated in the colons of TLR4(-/-) mice with acute DSS-induced colitis. An anti-MIF antibody significantly suppressed colitis and elevation of matrix metalloproteinase-13 in TLR4(-/-) mice. The current results obtained from TLR4(-/-) mice provide evidence that MIF plays a critical role in the development of acute DSS-induced colitis.
  Clinical & Experimental Immunology 10/2005; 141(3):412-21. · 3.36 Impact Factor
• Article: Transgenic over-expression of macrophage migration inhibitory factor renders mice markedly more susceptible to experimental colitis.

  T Ohkawara, K Miyashita, J Nishihira, K Mitsuyama, H Takeda, M Kato, N Kondo, Y Yamasaki, M Sata, T Yoshiki, T Sugiyama, M Asaka
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  ABSTRACT: Enhanced production of macrophage migration inhibitory factor (MIF) is recognized in patients with inflammatory bowel disease (IBD) and mice with experimental colitis; however, the precise molecular function of MIF in colitis is not fully understood. To further investigate this matter, we examined the pathological features of MIF transgenic mice with dextran sulphate sodium (DSS)-induced colitis. We generated transgenic mice carrying a murine MIF cDNA driven by a cytomegalovirus enhancer and a beta-actin/beta-globin promoter. Mice were orally administered 1-4% DSS in drinking water for 7 days. Clinical disease activity, survival and histological features were evaluated. The level of myeloperoxidase (MPO) activity in the colon tissue was measured to assess neutrophil infiltration. The level of corticosterone in the serum was measured by enzyme linked-immunosorbent assay (ELISA). MIF mRNA and protein were markedly up-regulated in the colon and serum obtained from MIF transgenic mice. The severity of the colitis induced by 1% DSS treatment was markedly higher in MIF transgenic mice than in wild-type mice. We also found that MPO activity was significantly higher in MIF transgenic mice than wild-type mice in response to DSS stimulation. Interestingly, the corticosterone level remained unchanged in MIF transgenic mice. MIF enhances DSS-induced colitis, in part via neutrophil accumulation and inhibition of glucocorticoid bioactivity.
  Clinical & Experimental Immunology 06/2005; 140(2):241-8. · 3.36 Impact Factor
• Article: [The role of macrophage migration inhibitory factor (MIF) for dextran sulfate sodium-induced colitis in mice].

  T Ohkawara
  [Hokkaido igaku zasshi] The Hokkaido journal of medical science 08/2001; 76(4):215-24.