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Publication
Featured researches published by Kunihiko Ikehara.
Human Gene Therapy | 2001
Satoshi Inoue; Motoyoshi Suzuki; Yoji Nagashima; Shunsuke Suzuki; Tomonori Hashiba; Takahiro Tsuburai; Kunihiko Ikehara; Takeshi Matsuse; Yoshiaki Ishigatsubo
By using a direct, intratracheal inoculation of an adenovirus encoding heme oxygenase 1 (Ad.HO-1), model gene therapy for acute lung injury induced by inhaled pathogen was performed. Data demonstrated that Ad.HO-1 administration is as effective as the pharmacologic upregulation of the endogenous HO-1 gene expression by hemin to attenuate neutrophilic inflammations of the lung after aerosolized lipopolysaccharide (LPS) exposure. Interestingly, immunohistochemical analysis revealed that the HO-1 gene was transferred not only to the airway epithelium, but to the alveolar macrophages (AMs). Moreover, overexpression of exogenous HO-1 in the macrophages provided a high level of endogenous interleukin 10 (IL-10) production from the macrophages, and additional experiments using IL-10 knockout mice demonstrated that the increase in IL-10 in the macrophages was critical for the resolution of neutrophilic migration in the lung after LPS exposure. These results suggest that AMs not only are barriers for efficient gene transfer to the respiratory epithelium, but also represent logical targets for Ad-mediated, direct, in vivo gene therapy strategies for inflammatory disorders in humans.
Human Gene Therapy | 2002
Takahiro Tsuburai; Motoyoshi Suzuki; Yoji Nagashima; Shunsuke Suzuki; Satoshi Inoue; Tomonori Hashiba; Atsuhisa Ueda; Kunihiko Ikehara; Takeshi Matsuse; Yoshiaki Ishigatsubo
Heme oxygenase 1 (HO-1) is an inducible enzyme that catalyzes heme to generate bilirubin, ferritin, and carbon monoxide. Because enhanced expression of HO-1 confers protection against many types of cell and tissue damage by modulating apoptotic cell death or cytokine expression profiles, we hypothesized that adenovirus-mediated transfer of HO-1 cDNA and subsequent overexpression of the protein in lung would provide therapeutic benefit in a murine model of bleomycin-induced pulmonary fibrosis. In C57BL/6 mice, HO-1 overexpression clearly suppressed the development of fibrotic changes and was associated with enhanced interferon gamma production in lung and reduced numbers of respiratory epithelial cells with damaged DNA. However, HO-1 overexpression did not prevent pulmonary fibrosis induced by agonistic anti-Fas antibody inhalation in C57BL/6 or ICR mice, a strain known to develop pulmonary fibrosis via the Fas-Fas ligand (FasL) pathway. Consistent with the concept that HO-1 overexpression prevents fibrosis via a pathway independent of Fas-FasL interaction, Ad.HO-1 administration prevented bleomycin-induced pulmonary fibrosis in gld/gld mice, which express nonfunctional FasL. These observations suggest that using HO-1 overexpression strategies to treat idiopathic pulmonary fibrosis, or fibrotic disorders of other target organs, by attenuating apoptotic cell death likely would be effective in clinical situations.
Allergology International | 2007
Takahiro Tsuburai; Naomi Tsurikisawa; Masami Taniguchi; Sonoko Morita; Emiko Ono; Chiyako Oshikata; Mamoru Ohtomo; Yuji Maeda; Kunihiko Ikehara; Kazuo Akiyama
The journal of the Japanese Respiratory Society | 2003
Akihiro Tagawa; Kunihiko Ikehara; Takahiro Tsuburai; Harumi Nishiyama; Miyazawa N; Hashiba T; Suzuki M; Shunsuke Suzuki; Yoshiaki Ishigatsubo
Allergology International | 2008
Takahiro Tsuburai; Naomi Tsurikisawa; Sonoko Morita; Hideki Hasunuma; Hiroshi Kanegae; Yasushi Ishimaru; Yuma Fukutomi; Hidenori Tanimoto; Emiko Ono; Chiyako Oshikata; Kiyoshi Sekiya; Otomo M; Yuji Maeda; Masami Taniguchi; Kunihiko Ikehara; Kazuo Akiyama
The journal of the Japanese Respiratory Society | 2008
Chiyako Oshikata; Takahiro Tsuburai; Naomi Tsurikisawa; Emiko Ono; Ai Higashi; Yuma Fukutomi; Hidenori Tanimoto; Kiyoshi Sekiya; Otomo M; Yuji Maeda; Masami Taniguchi; Kunihiko Ikehara; Kazuo Akiyama
Allergology International | 2009
Takahiro Tsuburai; Naomi Tsurikisawa; Sayaka Tatsuno; Yuma Fukutomi; Hidenori Tanimoto; Emiko Ono; Chiyako Oshikata; Kiyoshi Sekiya; Otomo M; Yuji Maeda; Masami Taniguchi; Kunihiko Ikehara; Kazuo Akiyama
The journal of the Japanese Respiratory Society | 2003
Takahiro Tsuburai; Kunihiko Ikehara; Shunsuke Suzuki; Takeshi Shinohara; Mishima W; Akihiro Tagawa; Itou M; Miyazawa N; Harumi Nishiyama; Akira Shoji; Suzuki M; Takeshi Matsuse; Yoshiaki Ishigatsubo
The journal of the Japanese Respiratory Society | 2007
Takahiro Tsuburai; Suzuki S; Naomi Tsurikisawa; Higashi N; Ai Higashi; Chiyako Oshikata; Emiko Ono; Morita S; Ohtomo M; Yuji Maeda; Kunihiko Ikehara; Masami Taniguchi; Kazuo Akiyama
The journal of the Japanese Respiratory Society | 2003
Akihiro Tagawa; Kunihiko Ikehara; Harumi Nishiyama; Takahiro Tsuburai; Takeshi Shinohara; Nobuko Kusano; Tomohisa Baba; Akira Shoji; Takeshi Kaneko; Shunsuke Suzuki; Yoshiaki Ishigatsubo