SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice
Abstract.: 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) hyperresponsivenes...
| 發表在: | Journal of Pharmacological Sciences |
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| Main Authors: | , , , |
| 格式: | Article |
| 語言: | 英语 |
| 出版: |
Elsevier
2010-01-01
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| 在線閱讀: | http://www.sciencedirect.com/science/article/pii/S1347861319308424 |
| _version_ | 1849314699646074880 |
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| author | Yoshihiko Chiba Hiroki Takeuchi Hiroyasu Sakai Miwa Misawa |
| author_facet | Yoshihiko Chiba Hiroki Takeuchi Hiroyasu Sakai Miwa Misawa |
| author_sort | Yoshihiko Chiba |
| collection | DOAJ |
| container_title | Journal of Pharmacological Sciences |
| description | Abstract.: 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. Keywords:: sphingosine kinase, sphingosine-1-phosphate, bronchial smooth muscle, airway hyperresponsiveness, allergic bronchial asthma |
| format | Article |
| id | doaj-art-e6ae9bc548fb45a787bb061c62ca01a6 |
| institution | Directory of Open Access Journals |
| issn | 1347-8613 |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-e6ae9bc548fb45a787bb061c62ca01a62025-09-03T02:41:22ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-01114330431010.1254/jphs.10202FPSKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in MiceYoshihiko Chiba0Hiroki Takeuchi1Hiroyasu Sakai2Miwa Misawa3Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan; Corresponding author. chiba@hoshi.ac.jpDepartment of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, JapanDepartment of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, JapanDepartment of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, JapanAbstract.: 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. Keywords:: sphingosine kinase, sphingosine-1-phosphate, bronchial smooth muscle, airway hyperresponsiveness, allergic bronchial asthmahttp://www.sciencedirect.com/science/article/pii/S1347861319308424 |
| spellingShingle | Yoshihiko Chiba Hiroki Takeuchi Hiroyasu Sakai Miwa Misawa SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice |
| title | SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice |
| title_full | SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice |
| title_fullStr | SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice |
| title_full_unstemmed | SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice |
| title_short | SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice |
| title_sort | ski ii an inhibitor of sphingosine kinase ameliorates antigen induced bronchial smooth muscle hyperresponsiveness but not airway inflammation in mice |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319308424 |
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