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

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• 作者：Vani Mishra^a ; ^{vanimish@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Vikas Baranwal^a ; Rohit K. Mishra^b ; ^{rohit_ernet@yahoo.co.in" class="auth_mail" title="E-mail the corresponding author} ; Shivesh Sharma^b ; Bholanath Paul^c ; Avinash C. Pandey^a
• 关键词：nTiO2 ; Asthma ; NF-κB ; Socs3 ; Th2-type immune response
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：92
• 期：Complete
• 页码：90-102
• 全文大小：3219 K

文摘

Titanium dioxide nanoparticles (nTiO₂) 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 nTiO₂ 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-κB, with nTiO₂ as an adjuvant in mouse model of asthma. nTiO₂ 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-κB, IL-6 and TNF-α. Furthermore, transient in vivo blocking of NF-κB by NF-κB p65 siRNA, downregulated the expression of Socs3, IL-6 and TNF-α. Our study, thus, shows that nTiO₂ exacerbate the inflammatory responses in lungs of pre-sensitized allergic individuals and that these changes are regulated via NF-κB pathway.