Titanium dioxide nanoparticles augment allergic airway inflammation and Socs3 expression via NF-κB pathway in murine model of asthma

被引:48
|
作者
Mishra, Vani [1 ]
Baranwal, Vikas [1 ]
Mishra, Rohit K. [2 ]
Sharma, Shivesh [2 ]
Paul, Bholanath [3 ]
Pandey, Avinash C. [1 ]
机构
[1] Univ Allahabad, Nanotechnol Applicat Ctr, Allahabad 211002, Uttar Pradesh, India
[2] Motilal Nehru Natl Inst Technol, Ctr Med Diagnost & Res, Allahabad 211004, Uttar Pradesh, India
[3] Indian Inst Toxicol Res, Immunobiol Div, Lucknow 226001, Uttar Pradesh, India
关键词
nTiO(2); Asthma; NF-kappa B; Socs3; Th2-type immune response; ALVEOLAR MACROPHAGES; CYTOKINE SIGNALING-3; INHALATION EXPOSURE; MOLECULAR-MECHANISM; INDUCED APOPTOSIS; MOUSE MODEL; CELL-DEATH; LUNG; TIO2; PARTICLES;
D O I
10.1016/j.biomaterials.2016.03.016
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Titanium dioxide nanoparticles (nTiO(2)) previously considered to possess relatively low toxicity both in vitro and in vivo, although classified as possibly carcinogenic to humans. Also, their adjuvant potential has been reported to promote allergic sensitization and modulate immune responses. Previously, in OVA induced mouse model of asthma we found high expression of Socs3 and low expression of Stat3 and IL-6. However, a clear understanding regarding the signaling pathways associated with nTiO(2) adjuvant effect in mouse model of asthma is lacking. In the present study we investigated the status of Stat3/IL-6 and Socs3 and their relationship with NF-kappa B, with nTiO(2) as an adjuvant in mouse model of asthma. nTiO(2) when administered with ovalbumin (OVA) during sensitization phase augmented airway hyper responsiveness (AHR), biochemical markers of lung damage and a mixed Th2/Th1 dependent immune response. At the same time, we observed significant elevation in the levels of Stat3, Socs3, NF-kappa B, IL-6 and TNF-alpha. Furthermore, transient in vivo blocking of NF-kappa B by NF-kappa B p65 siRNA, downregulated the expression of Socs3, IL-6 and TNF-alpha. Our study, thus, shows that nTiO(2) exacerbate the inflammatory responses in lungs of pre-sensitized allergic individuals and that these changes are regulated via NF-kappa B pathway. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:90 / 102
页数:13
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