2013 Fiscal Year Final Research Report
Effetct of Pseudomonas aeruginosa-derived neutral ceramidase on immunological responses of three-dimensionally cultured human primary keratinocytes
| Project/Area Number |
24659293
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Pain science
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SUGA Yasushi 順天堂大学, 大学院医学研究科, 教授 (90245738)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | アトピー性皮膚炎 / 緑膿菌 / セラミダーゼ / ケラチノサイト / スフィンゴシン1リン酸 / 炎症性サイトカイン |
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| Research Abstract |
A Pseudomonas aeruginosa-derived neutral ceramidase (PaCDase) isolated from a patient with atopic dermatitis was shown to effectively degrade ceramide. The ceramide metabolite sphingosine-1-phosphate (S1P) stimulated the production of inflammatory mediators such as TNF and IL-8 from three-dimensionally cultured human primary keratinocytes (3D keratinocytes). PaCDase induced the production of TNF and IL-8, and this production was dependent on ceramidase enzymatic activity. S1P enhanced the gene expression of TNF and IL-8, and this enhancement was inhibited by a sphingosine kinase inhibitor and an S1P receptor antagonist. The TNF-binding antibody infliximab suppressed the PaCDase-induced upregulation of IL-8 mRNA but not of TNF mRNA. These findings suggest that, 3D keratinocytes produce S1P from sphingosine, which is produced through the hydrolysis of ceramide by PaCDase, and then S1P induced TNF production from these cells, resulted in production of IL-8.
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[Journal Article] Pseudomonas-derived ceramidase induces production of inflammatory mediators from human keratinocytes via sphingosine-1-phosphate2014
Author(s)
Oizumi A, Nakayama H, Okino N, Iwahara C, Kina K, Matsumoto R, Ogawa H, Takamori K, Ito M, Suga Y, Iwabuchi K.
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