title: Titanium dioxide nanoparticles augment allergic airway inflammation and Socs3 expression via NF-κB pathway in murine model of asthma.
abstract: 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.
authors.affiliation: Nanotechnology Application Centre, University of Allahabad, Allahabad 211002, India. Electronic address: vanimish@gmail.com.
authors.forename: Vani
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Nanotechnology Application Centre, University of Allahabad, Allahabad 211002, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Baranwal
authors.affiliation: Centre for Medical Diagnostic and Research, Motilal Nehru National Institute of Technology, Allahabad 211004, India. Electronic address: rohit_ernet@yahoo.co.in.
authors.forename: Rohit K
authors.initials: RK
authors.lastname: Mishra
authors.affiliation: Centre for Medical Diagnostic and Research, Motilal Nehru National Institute of Technology, Allahabad 211004, India.
authors.forename: Shivesh
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Immunobiology Division, Indian Institute of Toxicology Research, Lucknow 226001, India.
authors.forename: Bholanath
authors.initials: B
authors.lastname: Paul
authors.affiliation: Nanotechnology Application Centre, University of Allahabad, Allahabad 211002, India.
authors.forename: Avinash C
authors.initials: AC
authors.lastname: Pandey
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D006967:Hypersensitivity / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010047:Ovalbumin; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014025:Titanium / Q000737:chemistry*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein; C009495:titanium dioxide; D010047:Ovalbumin; D014025:Titanium
keywords: Asthma; NF-κB; Socs3; Th2-type immune response; nTiO(2)