Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation

被引:14
作者
Aguilera-Aguirre, Leopoldo [1 ]
Hao, Wenging [1 ]
Pan, Lang [1 ]
Li, Xiaoxue [1 ]
Saavedra-Molina, Alfredo [1 ]
Bacsi, Attila [1 ]
Radak, Zsolt [1 ]
Sur, Sanjiv [2 ,3 ,4 ]
Brasier, Allan R. [2 ,3 ,4 ]
Ba, Xueqing [1 ]
Boldogh, Istvan [1 ,4 ]
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.
引用
收藏
页码:L1058 / L1068
页数:11
相关论文
共 65 条
[1]   Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling [J].
Aguilera-Aguirre, Leopoldo ;
Hosoki, Koa ;
Bacsi, Attila ;
Radak, Zsolt ;
Sur, Sanjiv ;
Hegde, Muralidhar L. ;
Tian, Bing ;
Saavedra-Molina, Alfredo ;
Brasier, Allan R. ;
Ba, Xueqing ;
Boldogh, Istvan .
FREE RADICAL BIOLOGY AND MEDICINE, 2015, 89 :20-33
[2]   Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes [J].
Aguilera-Aguirre, Leopoldo ;
Hosoki, Koa ;
Bacsi, Attila ;
Radak, Zsolt ;
Wood, Thomas G. ;
Widen, Steven G. ;
Sur, Sanjiv ;
Ameredes, Bill T. ;
Saavedra-Molina, Alfredo ;
Brasier, Allan R. ;
Ba, Xueqing ;
Boldogh, Istvan .
FREE RADICAL BIOLOGY AND MEDICINE, 2015, 81 :107-118
[3]   Innate Inflammation Induced by the 8-Oxoguanine DNA Glycosylase-1-KRAS-NF-κB Pathway [J].
Aguilera-Aguirre, Leopoldo ;
Bacsi, Attila ;
Radak, Zsolt ;
Hazra, Tapas K. ;
Mitra, Sankar ;
Sur, Sanjiv ;
Brasier, Allan R. ;
Ba, Xueqing ;
Boldogh, Istvan .
JOURNAL OF IMMUNOLOGY, 2014, 193 (09) :4643-4653
[4]   Mitochondrial Dysfunction Increases Allergic Airway Inflammation [J].
Aguilera-Aguirre, Leopoldo ;
Bacsi, Attila ;
Saavedra-Molina, Alfredo ;
Kurosky, Alexander ;
Sur, Sanjiv ;
Boldogh, Istvan .
JOURNAL OF IMMUNOLOGY, 2009, 183 (08) :5379-5387
[5]   Small Non-Coding RNAs: New insights in Modulation of Host immune Response by intracellular Bacterial Pathogens [J].
Ahmed, Waqas ;
Zheng, Ke ;
Liu, Zheng-Fei .
FRONTIERS IN IMMUNOLOGY, 2016, 7
[6]   The roles of miRNAs as potential biomarkers in lung diseases [J].
Alipoor, Shamila D. ;
Adcock, Ian M. ;
Garssen, Johan ;
Mortaz, Esmaeil ;
Varahram, Mohammad ;
Mirsaeidi, Mehdi ;
Velayati, Aliakbar .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2016, 791 :395-404
[7]   Airway injury as a mechanism for exercise-induced bronchoconstriction in elite athletes [J].
Anderson, Sandra D. ;
Kippelen, Pascale .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2008, 122 (02) :225-235
[8]   8-Oxoguanine DNA glycosylase-1-driven DNA base excision repair: role in asthma pathogenesis [J].
Ba, Xueqing ;
Aguilera-Aguirre, Leopoldo ;
Sur, Sanjiv ;
Boldogh, Istvan .
CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY, 2015, 15 (01) :89-97
[9]   8-Oxoguanine DNA Glycosylase-1 Augments Proinflammatory Gene Expression by Facilitating the Recruitment of Site-Specific Transcription Factors [J].
Ba, Xueqing ;
Bacsi, Attila ;
Luo, Jixian ;
Aguilera-Aguirre, Leopoldo ;
Zeng, Xianlu ;
Radak, Zsolt ;
Brasier, Allan R. ;
Boldogh, Istvan .
JOURNAL OF IMMUNOLOGY, 2014, 192 (05) :2384-2394
[10]   Effect of pollen-mediated oxidative stress on immediate hypersensitivity reactions and late-phase inflammation in allergic conjunctivitis [J].
Bacsi, A ;
Dharajiya, N ;
Choudhury, BK ;
Sur, S ;
Boldogh, I .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 116 (04) :836-843