title: Gold nanoparticles regulate the blimp1/pax5 pathway and enhance antibody secretion in B-cells.
abstract: Nanoparticles are potential threats to human health and the environment; however, their medical applications as drug carriers targeting cancer cells bring hope to contemporary cancer therapy. As a model drug carrier, gold nanoparticles (GNPs) have been investigated extensively for in vivo toxicity. The effect of GNPs on the immune system, however, has rarely been examined. Antibody-secreting cells were treated with GNPs with diameters ranging from 2 to 50 nm. The GNPs enhanced IgG secretion in a size-dependent manner, with a peak of efficacy at 10 nm. The immune-stimulatory effect reached a maximum at 12 h after treatment but returned to control levels 24 h after treatment. This enhancing effect was validated ex vivo using B-cells isolated from mouse spleen. Evidence from RT-PCR and western blot experiments indicates that GNP-treatment upregulated B-lymphocyte-induced maturation protein 1 (blimp1) and downregulated paired box 5 (pax5). Immunostaining for blimp1 and pax5 in B-cells confirmed that the GNPs stimulated IgG secretion through the blimp1/pax5 pathway. The immunization of mice using peptide-conjugated GNPs indicated that the GNPs were capable of enhancing humoral immunity in a size-dependent manner. This effect was consistent with the bio-distribution of the GNPs in mouse spleen. In conclusion, in vitro, ex vivo, and in vivo evidence supports our hypothesis that GNPs enhance humoral immunity in mouse. The effect on the immune system should be taken into account if nanoparticles are used as carriers for drug delivery. In addition to their toxicity, the immune-stimulatory activity of nanoparticles could play an important role in human health and could have an environmental impact.
authors.affiliation: Department of Materials Science and Engineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Lee
authors.forename: Shih-Han
authors.initials: SH
authors.lastname: Syu
authors.forename: Yu-Shiun
authors.initials: YS
authors.lastname: Chen
authors.forename: Saber M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Andrei
authors.initials: A
authors.lastname: Aleksandrovich Onischuk
authors.forename: Wen Liang
authors.initials: WL
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Steven Huang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology*; D006046:Gold / Q000276:immunology*; D053768:Metal Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D010455:Peptides; C513258:Prdm1 protein, mouse; D014157:Transcription Factors; D006046:Gold; D000074462:Positive Regulatory Domain I-Binding Factor 1