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Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation
被引:14
作者:

Aguilera-Aguirre, Leopoldo
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机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Hao, Wenging
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Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Pan, Lang
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Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Li, Xiaoxue
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h-index: 0
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Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Saavedra-Molina, Alfredo
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Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Bacsi, Attila
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Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Radak, Zsolt
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Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Sur, Sanjiv
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机构:
Univ Texas Med Branch, Div Endocrinol, Dept Internal Med, Galveston, TX 77555 USA
Univ Texas Med Branch, Div Allergy & Immunol, Dept Internal Med, Galveston, TX 77555 USA
Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Brasier, Allan R.
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h-index: 0
机构:
Univ Texas Med Branch, Div Endocrinol, Dept Internal Med, Galveston, TX 77555 USA
Univ Texas Med Branch, Div Allergy & Immunol, Dept Internal Med, Galveston, TX 77555 USA
Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Ba, Xueqing
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机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA

Boldogh, Istvan
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h-index: 0
机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA
Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA
机构:
[1] Univ Texas Med Branch, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA
[2] Univ Texas Med Branch, Div Endocrinol, Dept Internal Med, Galveston, TX 77555 USA
[3] Univ Texas Med Branch, Div Allergy & Immunol, Dept Internal Med, Galveston, TX 77555 USA
[4] Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA
基金:
匈牙利科学研究基金会;
中国国家自然科学基金;
关键词:
DNA repair;
cell signaling;
allergy;
micro-RNAs;
BASE-EXCISION-REPAIR;
EPITHELIAL-MESENCHYMAL TRANSITION;
TRANSCRIPTOME ANALYSIS REVEALS;
AIRWAY INFLAMMATION;
ASTHMA PATHOGENESIS;
GENE-EXPRESSION;
PULMONARY-FIBROSIS;
MAMMALIAN-CELLS;
8-OXOGUANINE;
GLYCOSYLASE;
D O I:
10.1152/ajplung.00141.2017
中图分类号:
Q4 [生理学];
学科分类号:
071003 ;
摘要:
A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant forms of oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase 1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known. Here, we postulate that the OGG1 signaling pathway differentially altered the levels of small regulatory RNAs and increased the expression of T helper 2 (Th2) cytokines in ragweed pollen extract (RWPE)-challenged lungs. To determine this, the lungs of sensitized mice expressing or lacking OGG1 were challenged with RWPE and/or with OGG1's excision product 8-oxoG. The responses in lungs were assessed by next-generation sequencing, as well as various molecular and histological approaches. The results showed that RWPE challenge induced oxidative burst and damage to DNA and activated OGG1 signaling, resulting in the differential expression of 84 micro-RNAs (miRNAs), which then exacerbated antigen-driven allergic inflammation and histological changes in the lungs. The exogenous administration of the downregulated let-7b-p3 mimetic or inhibitors of upregulated miR-23a or miR-27a decreased eosinophil recruitment and mucus and collagen production via controlling the expression of IL-4, IL-5, and IL-13. Together, these data demonstrate the roles of OGG1 signaling in the regulation of antigen-driven allergic immune responses via differential expression of miRNAs upstream of Th2 cytokines and eosinophils.
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收藏
页码:L1058 / L1068
页数:11
相关论文
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Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
Univ Texas Med Branch, Sealy Ctr Mol Med, Sch Med, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
[9]
8-Oxoguanine DNA Glycosylase-1 Augments Proinflammatory Gene Expression by Facilitating the Recruitment of Site-Specific Transcription Factors
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Ba, Xueqing
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Bacsi, Attila
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Luo, Jixian
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Aguilera-Aguirre, Leopoldo
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Zeng, Xianlu
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Radak, Zsolt
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Brasier, Allan R.
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Boldogh, Istvan
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JOURNAL OF IMMUNOLOGY,
2014, 192 (05)
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Ba, Xueqing
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
NE Normal Univ, Inst Genet & Cytol, Key Lab Mol Epigenet, Changchun 130024, Peoples R China Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Bacsi, Attila
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Luo, Jixian
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Aguilera-Aguirre, Leopoldo
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Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Zeng, Xianlu
论文数: 0 引用数: 0
h-index: 0
机构:
NE Normal Univ, Inst Genet & Cytol, Key Lab Mol Epigenet, Changchun 130024, Peoples R China Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Radak, Zsolt
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Brasier, Allan R.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA
Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA

Boldogh, Istvan
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
Univ Texas Med Branch, Sealy Ctr Mol Med, Galveston, TX 77555 USA Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA
[10]
Effect of pollen-mediated oxidative stress on immediate hypersensitivity reactions and late-phase inflammation in allergic conjunctivitis
[J].
Bacsi, A
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Dharajiya, N
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Choudhury, BK
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Sur, S
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Boldogh, I
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JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY,
2005, 116 (04)
:836-843

Bacsi, A
论文数: 0 引用数: 0
h-index: 0
机构: Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA

Dharajiya, N
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h-index: 0
机构: Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA

Choudhury, BK
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h-index: 0
机构: Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA

Sur, S
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h-index: 0
机构: Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA

Boldogh, I
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h-index: 0
机构: Univ Texas, Dept Microbiol & Immunol, Med Branch, Galveston, TX 77555 USA