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  1. 医歯学総合研究科
  2. 医歯学総合研究科・博士論文

Human neutrophil peptides induce interleukin-8 in intestinal cells through the P2 receptor and ERK1/2 signaling pathways

http://hdl.handle.net/10232/25558
http://hdl.handle.net/10232/25558
e354acb0-287e-4f13-a420-7f18779b91e5
名前 / ファイル ライセンス アクション
Diss_指宿_和成_ISK338_2015.pdf Diss_指宿_和成_ISK338_2015.pdf (557.9 kB)
Abstract_指宿_和成_458800020_2015.pdf Abstract_指宿_和成_458800020_2015.pdf (22.8 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2016-07-07
タイトル
タイトル Human neutrophil peptides induce interleukin-8 in intestinal cells through the P2 receptor and ERK1/2 signaling pathways
著者 指宿, 和成

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WEKO 124228

指宿, 和成

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著者よみ
姓名 イブスキ, カズナリ
別言語の著者
姓名 IBUSUKI, Kazunari
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
要約(Abstract)
内容記述タイプ Other
内容記述 Abstract. Human neutrophil peptides (HNPs) are antimicrobial peptides produced predominantly by neutrophils. We have previously reported that HNP 1-3 levels are increased in the sera and plasma of patients with active ulcerative colitis. The increased expression of interleukin-8 (IL-8) has also been demonstrated in the colonic mucosa of patients with active ulcerative colitis. HNPs induce IL-8 in lung epithelial cells and monocytes through the P2Y6 signaling pathway. However, the association between HNPs and IL-8 in the intestinal mucosa has not yet been investigated. In the present study, we investigated the effects of HNP-1 on the production of IL-8 by human intestinal epithelial cells and the underlying signaling mechanisms. We observed a significant increase in IL-8 expression in the human colon carcinoma cell line, Caco-2, following treatment with HNP-1. The non-selective P2 receptor antagonists, suramin and pyridoxal phosphate-6-azo (benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), significantly blocked the HNP-1-induced expression of IL-8 in the Caco-2 cells. The P2Y6-specific antagonist, MRS2578, led to a significant but partial decrease in IL-8 expression, suggesting that P2 receptors in addition to P2Y6 are involved in the HNP-1-induced production of IL-8 by Caco-2 cells. In agreement with this finding, HNP-1 also significantly increased IL-8 production in the P2Y6-negative human colon cancer cell line, HT-29, and this increase was blocked by treatment with suramin and PPADS. HNP-1 significantly increased the phosphorylation of extracellular signal-regulated kinase 1/2(ERK1/2) and p38 mitogen-activated protein kinase (MAPK) in the HT-29 cells. However, the HNP-1-induced production of IL-8 was suppressed by the ERK1/2 inhibitor, U0126, but not by the p38 MAPK inhibitor, SB 203580. In conclusion, our data demonstrate that HNP-1 induces IL-8 production not only through P2Y6, but also through additional P2 receptors via an ERK1/2-dependent mechanism in intestinal epithelial cells.
要約(Abstract)
内容記述タイプ Other
内容記述 Kazunari Ibusuki, Toshio Sakiyama, Shuji Kanmura, Takuro Maeda, Yuji Iwa shita, Yuichiro Nasu, Fumisato Sasaki, Hiroki Taguchi, Shinichi Hashimoto, Masat sugu Numata, Hirofumi Uto, Hirohito Tsubouchi and Akio Ido
Human neutrophil peptides induce interleukin-8 in intestinal epithelial cells through the P2 receptor and ERK1/2 signaling pathways
International Journal of Molecular Medicine, 2015, 35(6), p.1603-1609
https://doi.org/10.3892/ijmm.2015.2156
作成日
日付 2015-10-27
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
NDC
主題Scheme NDC
主題 490
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文全文
ファイル(説明)
内容記述タイプ Other
内容記述 博士論文要旨
公開者・出版者
出版者 Spandidos Publications
公開者・出版者
出版者 鹿児島大学
公開者よみ
公開者よみ カゴシマ ダイガク
公開者別名
公開者別名 Kagoshima University
備考
備考 【指導教員:井戸章雄】
date.appl
【学位申請日】2015-05-07
学位名
学位名 博士(医学)Doctor of Philosophy in Medical Science
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 17701
学位授与機関名 鹿児島大学
学位授与年月日
学位授与年月日 2015-08-24
学位授与番号
学位授与番号 甲総研第338号
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