Induction of inflammatory responses and gene expression by intratracheal instillation of silver nanoparticles in mice

The adverse effects of silver nanoparticles (AgNPs) to human and environment have not been known well, although AgNPs are now widely applicated to consumer products. In this study, we investigated the inflammatory responses including cytokine production and gene expression in mice after a single intratracheal instillation of AgNPs. As results, pro-inflammatory cytokines (IL-1, TNF-a, and IL-6) and Th0 cytokine (IL-2) were progressively increased by the day 28 after a single instillation. The secretion of Th2 type cytokine was more dominant than that of Th1 type cytokine, and the increase of B cell distribution was also observed. But, histopathological changes in lung were observed only at day 1 after instillation. We identified the changes of gene expression induced by AgNPs in lung tissue using microarray. The 261 genes related to inflammation and tissue damages including Saa3, Krt 13, Lor, Krtdap, and Lcn 2 were up-regulated by over 2 fold, while 103 genes including H2-Ea, Chka, BC030476, Heg1 and Hbb-b1 were down-regulated. Based on the data, it is suggested that AgNPs may induce Th2 type dominant inflammatory responses and tissue damage in the lung of mice.

[1]  Kyunghee Choi,et al.  Pro-inflammatory and potential allergic responses resulting from B cell activation in mice treated with multi-walled carbon nanotubes by intratracheal instillation. , 2009, Toxicology.

[2]  H. Takahashi,et al.  Loricrin and human skin diseases: molecular basis of loricrin keratodermas. , 1998, Histology and histopathology.

[3]  R. T. Kintz,et al.  Absence of toxic effects in silver reclamation workers. , 1989, Scandinavian journal of work, environment & health.

[4]  M. Hande,et al.  Anti-proliferative activity of silver nanoparticles , 2009, BMC Cell Biology.

[5]  S. Hsu,et al.  Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. , 2009, Small.

[6]  M. Fasshauer,et al.  The adipokine SAA3 is induced by interleukin‐1β in mouse adipocytes , 2008, Journal of cellular biochemistry.

[7]  Acute silver poisoning through inhalation. , 1983, Bulletin of the Institute of Maritime and Tropical Medicine in Gdynia.

[8]  Evangelia Vlachou,et al.  The safety of nanocrystalline silver dressings on burns: a study of systemic silver absorption. , 2007, Burns : journal of the International Society for Burn Injuries.

[9]  K. Paknikar,et al.  Interactions of silver nanoparticles with primary mouse fibroblasts and liver cells. , 2009, Toxicology and applied pharmacology.

[10]  R. Fariss,et al.  Expression analysis of human pterygium shows a predominance of conjunctival and limbal markers and genes associated with cell migration , 2009, Molecular vision.

[11]  P. Baron,et al.  Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. , 2005, American journal of physiology. Lung cellular and molecular physiology.

[12]  U. Vogel,et al.  Lack of acute phase response in the livers of mice exposed to diesel exhaust particles or carbon black by inhalation , 2009, Particle and Fibre Toxicology.

[13]  Tung-Sheng Shih,et al.  The apoptotic effect of nanosilver is mediated by a ROS- and JNK-dependent mechanism involving the mitochondrial pathway in NIH3T3 cells. , 2008, Toxicology letters.

[14]  Tingfei Xi,et al.  [Status of biological evaluation on silver nanoparticles]. , 2008, Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi.

[15]  X. Chen,et al.  Nanosilver: a nanoproduct in medical application. , 2008, Toxicology letters.

[16]  B. Katzenellenbogen,et al.  Differential estradiol and selective estrogen receptor modulator (SERM) regulation of Keratin 13 gene expression and its underlying mechanism in breast cancer cells , 2008, Molecular and Cellular Endocrinology.

[17]  J. Jung,et al.  Twenty-Eight-Day Inhalation Toxicity Study of Silver Nanoparticles in Sprague-Dawley Rats , 2007, Inhalation toxicology.

[18]  J. James,et al.  Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. , 2003, Toxicological sciences : an official journal of the Society of Toxicology.

[19]  I. Yu,et al.  Subchronic inhalation toxicity of silver nanoparticles. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  M. Hande,et al.  Cytotoxicity and genotoxicity of silver nanoparticles in human cells. , 2009, ACS nano.

[21]  R. L. Jones,et al.  Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. , 2008, The journal of physical chemistry. B.

[22]  D. Hohl.  Expression patterns of loricrin in dermatological disorders. , 1993, The American Journal of dermatopathology.

[23]  J. Schlager,et al.  DNA damage response to different surface chemistry of silver nanoparticles in mammalian cells. , 2008, Toxicology and applied pharmacology.

[24]  S. Meo,et al.  Health hazards of welding fumes. , 2003, Saudi medical journal.

[25]  Kerst Stelwagen,et al.  The acute-phase protein serum amyloid A3 is expressed in the bovine mammary gland and plays a role in host defence , 2009, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[26]  Cheng-Chung Chou,et al.  Single-walled carbon nanotubes can induce pulmonary injury in mouse model. , 2008, Nano letters.

[27]  J. Yi,et al.  Induction of chronic inflammation in mice treated with titanium dioxide nanoparticles by intratracheal instillation. , 2009, Toxicology.

[28]  Jeremy J. W. Chen,et al.  Titanium dioxide nanoparticles induce emphysema‐like lung injury in mice , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  P. Schechter,et al.  Effects of Nanocrystalline Silver (NPI 32101) in a Rat Model of Ulcerative Colitis , 2007, Digestive Diseases and Sciences.

[30]  G. Melino,et al.  A Novel Mutation in the Keratin 13 Gene Causing Oral White Sponge Nevus , 2001, Journal of dental research.

[31]  B. Anner,et al.  Potent and reversible interaction of silver with pure Na,K-ATPase and Na,K-ATPase-liposomes. , 1994, Biochimica et biophysica acta.

[32]  K. Chung,et al.  Effects of repeated silver nanoparticles exposure on the histological structure and mucins of nasal respiratory mucosa in rats. , 2008, Toxicology letters.