Nano-sized zinc oxide and silver, but not titanium dioxide, induce innate and adaptive immunity and antiviral response in differentiated THP-1 cells. Issue 7 (9th August 2017)

• Record Type: Journal Article
• Authors: Poon, Wing-Lam; Alenius, Harri; Ndika, Joseph; Fortino, Vittorio; Kolhinen, Vesa; Meščeriakovas, Arūnas; Wang, Mingfu; Greco, Dario; Lähde, Anna; Jokiniemi, Jorma; Lee, Jetty Chung-Yung; El-Nezami, Hani; Karisola, Piia
• Is Part Of: Nanotoxicology. Volume 11:Issue 7(2017)
• Page Start: 936
• Page End: 951
• Publication Date: 2017-08-09
• Subjects: ZnO -- Ag -- nanomaterials -- immune system -- transcriptomics; Toxicology -- Periodicals; 615.9
• DOI: 10.1080/17435390.2017.1382600
• Languages: English
• ISSNs: 1743-5390

Abstract

Abstract: Nano-sized metal oxides are currently the most manufactured nanomaterials (NMs), and are increasingly used in consumer products. Recent exposure data reveal a genuine potential for adverse health outcomes for a vast array of NMs, however the underlying mechanisms are not fully understood. To elucidate size-related molecular effects, differentiated THP-1 cells were exposed to nano-sized materials (n-TiO2, n-ZnO and n-Ag), or their bulk-sized (b-ZnO and b-TiO2 ) or ionic (i-Ag) counterparts, and genome-wide gene expression changes were studied at low-toxic concentrations (<15% cytotoxicity). TiO2 materials were nontoxic in MTT assay, inducing only minor transcriptional changes. ZnO and Ag elicited dose-dependent cytotoxicity, wherein ionic and particulate effects were synergistic with respect to n-ZnO-induced cytotoxicity. In gene expression analyzes, 6 h and 24 h samples formed two separate hierarchical clusters. N-ZnO and n-Ag shared only 3.1% and 24.6% differentially expressed genes (DEGs) when compared to corresponding control. All particles, except TiO2, activated various metallothioneins. At 6 h, n-Zn, b-Zn and n-Ag induced various immunity related genes associating to pattern recognition (including toll-like receptor), macrophage maturation, inflammatory response (TNF and IL-1beta), chemotaxis (CXCL8) and leucocyte migration (CXCL2-3 and CXCL14). After 24 h exposure, especially n-Ag induced the expression of genes related to virus recognition and type I interferon responses. These results strongly suggest that in addition to ionic effects mediated by metallothioneins, n-Zn and n-Ag induce expression of genes involved in several innate and adaptive immunity associated pathways, which are known to play crucial role in immuno-regulation. This raises the concern of safe use of metal oxide and metal nanoparticle products, and their biological effects.