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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/10232/25558e354acb0-287e-4f13-a420-7f18779b91e5
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Diss_指宿_和成_ISK338_2015.pdf (557.9 kB)
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Abstract_指宿_和成_458800020_2015.pdf (22.8 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 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 | |||||
| タイトル言語 | en | |||||
| 著者 |
指宿, 和成
× 指宿, 和成 |
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| 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 | ||||||
| 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. 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 |
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| 内容記述言語 | en | |||||
| 作成日 | ||||||
| 日付 | 2015-10-27 | |||||
| 日付タイプ | Collected | |||||
| 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 | 博士論文全文, 博士論文要旨 | |||||
| 公開者・出版者 | ||||||
| 出版者 | Spandidos Publications | |||||
| 出版者言語 | en | |||||
| 公開者・出版者 | ||||||
| 出版者 | 鹿児島大学 | |||||
| 出版者言語 | ja | |||||
| 備考 | ||||||
| 備考言語 | ja | |||||
| 備考 | 【指導教員:井戸章雄】 | |||||
| date.appl | ||||||
| appl | 【学位申請日】2015-05-07 | |||||
| 学位名 | ||||||
| 学位名の言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位名 | ||||||
| 学位名の言語 | en | |||||
| 学位名 | Doctor of Philosophy in Medical Science | |||||
| 学位授与機関名 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 17701 | |||||
| 学位授与機関名の言語 | ja | |||||
| 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 | |||||
