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学科主题: 临床医学
题名:
An Immunoprotective Privilege of Corneal Epithelial Stem Cells Against Th17 Inflammatory Stress by Producing Glial Cell-Derived Neurotrophic Factor
作者: Bian, Fang1,2; Qi, Hong1,3; Ma, Ping1,4; Zhang, Lili1; Yoon, Kyung-Chul1,5; Pflugfelder, Stephen C.1; Li, De-Quan1
关键词: Glial cell-derived neurotrophic factor ; Adult stem cell ; Immunoprotection ; Th17 ; Corneal epithelium
刊名: STEM CELLS
发表日期: 2010-12-01
DOI: 10.1002/stem.539
卷: 28, 期:12, 页:2172-2181
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
研究领域[WOS]: Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
关键词[WOS]: GDNF MESSENGER-RNA ; DESICCATING STRESS ; OCULAR SURFACE ; CYTOKINE EXPRESSION ; MAPK ACTIVATION ; IL-17 RECEPTOR ; TNF-ALPHA ; DRY EYE ; LIMBAL ; DIFFERENTIATION
英文摘要:

Adult stem cells are well known for their self-renewal and regenerative capacity. The mechanisms protecting these cells from inflammatory damage have not been well elucidated. This study investigated the immunoprotective properties of corneal epithelial stem cells from inflammation by producing glial cell-derived neurotrophic factor (GDNF). Primary human limbal epithelial cells (HLECs) cultured from limbal explants were treated with interleukin (IL)-17A, tumor necrosis factor (TNF)-alpha, or hyperosmotic media, with or without GDNF or nuclear factor kappa B (NF-kappa B) inhibitor (NF-kappa B-I) for 4-48 hours. Inflammatory mediators and Th17-inducing cytokines were determined by real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunobead assays. NF-kappa B activation was detected by p65 phosphorylation, immunostaining and Western blotting. GDNF and its receptor, GDNF family receptor alpha-1, were exclusively immunolocalized in the basal layer of limbal epithelium, whereas IL-17 receptor was negative in these cells. Exogenous IL-17A stimulated the expression and production of inflammatory cytokines (TNF-alpha, IL-6, and IL-1 beta) and chemokine IL-8 by HLECs. Th17-inducing cytokines, transforming growth factor (TGF)-beta 1, IL-6, IL-23, and IL-1 beta, were significantly increased at mRNA and protein levels by HLECs exposed to TNF-alpha or hyperosmotic media. IL-17 activated NF-kappa B by p65 phosphorylation at serine 536 and nuclear translocation. GDNF or NF-kappa B-I blocked IL-17-induced NF-kappa B p65 activation and production of inflammatory mediators. Furthermore, GDNF suppressed the production of Th17-inducing cytokines through inhibiting NF-kappa B activation. These findings demonstrate that limbal progenitor cell-produced neurotrophic factor GDNF suppresses IL-17-mediated inflammation via NF-kappa B signaling pathway. This may represent a unique immunoprotective property of limbal stem cells against inflammatory challenges on the ocular surface. STEM CELLS 2010; 28: 2172-2181

语种: 英语
所属项目编号: FY06 PR064719 ; EY11915 ; 30872813
项目资助者: Department of Defense CDMRP PRMRP ; National Institutes of Health ; National Natural Science Foundation of China ; Research to Prevent Blindness ; Oshman Foundation ; William Stamps Farish Fund
WOS记录号: WOS:000285742700007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64911
Appears in Collections:北京大学第三临床医学院_眼科_期刊论文

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作者单位: 1.Baylor Coll Med, Ocular Surface Ctr, Cullen Eye Inst, Dept Ophthalmol, Houston, TX 77030 USA
2.Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Ophthalmol, Wuhan 430074, Peoples R China
3.Peking Univ, Hosp 3, Dept Ophthalmol, Beijing 100871, Peoples R China
4.Shandong Univ, Prov Hosp, Dept Ophthalmol, Jinan 250100, Peoples R China
5.Chonnam Natl Univ Med Sch & Hosp, Dept Ophthalmol, Kwangju, South Korea

Recommended Citation:
Bian, Fang,Qi, Hong,Ma, Ping,et al. An Immunoprotective Privilege of Corneal Epithelial Stem Cells Against Th17 Inflammatory Stress by Producing Glial Cell-Derived Neurotrophic Factor[J]. STEM CELLS,2010,28(12):2172-2181.
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