SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice
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概要
- 論文の詳細を見る
To determine if endogenously generated sphingosine-1-phosphate (S1P) is involved in the development of allergic bronchial asthma, the effects of systemic treatments with SKI-II, a specific inhibitor of sphingosine kinase, on antigen-induced bronchial smooth muscle (BSM) hyperresponsiveness and airway inflammation were examined in mice. Male BALB/c mice were actively sensitized with ovalbumin (OA) antigen and were repeatedly challenged with aerosolized antigen. Animals also received intraperitoneal injections with SKI-II (50 mg/kg) 1 h prior to each antigen challenge. The acetylcholine (ACh)-induced contraction of BSM isolated from the repeatedly antigen-challenged mice was significantly augmented, that is, BSM hyperresponsiveness, as compared with that from the control animals (P < 0.05). The BSM hyperresponsiveness induced by antigen exposure was ameliorated by the systemic treatment with SKI-II, whereas the treatments had no effect on BSM responsiveness to ACh in control animals. On the other hand, the systemic treatments with SKI-II had no effect on antigen-induced inflammatory signs, such as increase in cell counts in bronchoalveolar lavage fluids (BALFs) and change in airway histology; upregulation of BALF cytokines, such as interleukin-4 (IL-4) and IL-13; and elevation of total and OA-specific immunoglobulin E (IgE) in sera. These findings suggest that sphingosine kinase inhibitors such as SKI-II have an ability to prevent the development of BSM hyperresponsiveness, but not of allergic airway inflammation. The endogenously generated S1P might be one of the exacerbating factors for the airway hyperresponsiveness, one of the characteristic features of allergic bronchial asthma.
- 社団法人 日本薬理学会の論文
著者
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CHIBA Yoshihiko
Department of Pharmacology, School of Pharmacy, Hoshi University
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MISAWA Miwa
Department of Pharmacology, School of Pharmacy, Hoshi University
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SAKAI Hiroyasu
Department of Internal Medicine, Gifu University Graduate School of Medicine
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千葉 喜彦
山口大学理学部時間生物学研究室
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TAKEUCHI Hiroki
Department of Neurosurgery, Nagoya University School of Medicine
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Chiba Yoshihiko
Department Of Pharmacology School Of Pharmacy Hoshi University
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Misawa Miwa
Department Of Applied Pharmacology Hoshi University
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Sakai Hiroyasu
Department Of Pharmacology School Of Pharmacy Hoshi University
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Sakai H
Department Of Pharmaceutical Physiology Graduate School Of Medicine And Pharmaceutical Sciences Univ
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Takeuchi Hiroki
Department Of Neurosurgery Nagoya University School Of Medicine
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Sugitani Hideki
Department Of Clinical Chemistry Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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