title: Paraquat reduces natural killer cell activity via metallothionein induction.
abstract: Paraquat (PQ), one of the most widely used herbicides, has been used for several decades in agriculture. Some studies suggest that PQ has effects on the immune system. Moreover, previous studies have shown that PQ imparted some immunosuppressive effects. In the present study, cytotoxicity assays using splenic NK cells from mice treated for 28 days with PQ (at 0.2, 1, and 5 mg/kg) were performed to determine whether PQ altered the function of NK cells. Given that PQ was expected to induce an immunosuppressive effect, it was hypothesized that a gene involved in cellular metal ion homeostasis, metallothionein-1 (MT-1), could play an important role in this outcome. This belief was based on the fact that MT1 encodes a protein responsible for zinc ion homeostasis, and that a reduction in free zinc ion levels impairs NK cell function. The results showed that PQ treatments led to increased MT expression in several organs (liver, kidneys, testes) and in splenocytes, caused a reduction of both free zinc ions in sera and in free intracellular zinc, and reduced the expression of GATA-3, a zinc-finger transcription factor important for maturation and activity of T-cells and NK cells. These results provide a basis for a new molecular mechanism to describe potential immunosuppressive effects of PQ in vivo.
authors.affiliation: Department of Environmental & Health Chemistry, College of Pharmacy, Chung-Ang University , Seoul , South Korea.
authors.forename: Joo Hyuk
authors.initials: JH
authors.lastname: Lim
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Won
authors.forename: Kyong Hoon
authors.initials: KH
authors.lastname: Ahn
authors.forename: Moon Jung
authors.initials: MJ
authors.lastname: Back
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Fu
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Jang
authors.forename: Hae Chan
authors.initials: HC
authors.lastname: Ha
authors.forename: Yeo Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Dae Kyong
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D003603:Cytotoxins / Q000494:pharmacology; D050990:GATA3 Transcription Factor / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000276:immunology*; D051379:Mice; D010269:Paraquat / Q000494:pharmacology*; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D015032:Zinc / Q000276:immunology
chemical_list: D003603:Cytotoxins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007166:Immunosuppressive Agents; D008668:Metallothionein; D015032:Zinc; D010269:Paraquat
keywords: Immune response; NK cell; metallothionein; paraquat; pesticide