title: Effects of aspirin on expression of iron transport and storage proteins in BV-2 microglial cells.
abstract: In the light of recent studies, we hypothesized that aspirin might have the functions to regulate the expression of iron transport proteins and then affect cellular iron levels. To test this hypothesis, we investigated the effects of aspirin on expression of iron uptake protein transferrin receptor 1 (TfR1), iron release protein ferroportin 1 (Fpn1) and iron storage protein ferritin using Western blot analysis and on tumor necrosis factor (TNF)-αlpha, interleukin (IL)-6, interleukin (IL)-10 and hepcidin using quantitative real-time PCR in BV-2 microglial cells treated with lipopolysaccharides (LPS). We found that aspirin significantly down-regulated TfR1, while also up-regulated Fpn1 and ferritin expressions in BV-2 microglial cells in vitro. We also showed that TfR1 and Fpn1 expressions were significantly higher, while ferritin contents, IL-6, TNF-alpha and hepcidin mRNA levels were lower in cells treated with aspirin plus LPS than those in cells treated with LPS only. We concluded that aspirin has a negative effect on cell iron contents under 'normal' conditions and could partly reverse LPS-induced-disruption in cell iron balance under in vitro inflammatory conditions. Our findings also suggested that hepcidin might play a dominant role in the control of TfR1 expression by aspirin in the cells treated with LPS.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China.
authors.forename: Yan Xin
authors.initials: YX
authors.lastname: Xu
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors.forename: Li Rong
authors.initials: LR
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China; Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors.forename: Yu-Fu
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China.
authors.forename: Qian Qian
authors.initials: QQ
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science & Technology, Shanghai 200237, PR China; Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, PR China. Electronic address: qianzhongming@fudan.edu.cn.
authors.forename: Zhong Ming
authors.initials: ZM
authors.lastname: Qian
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. Electronic address: yake@cuhk.edu.hk.
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D005293:Ferritins / Q000096:biosynthesis; D064451:Hepcidins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D027682:Cation Transport Proteins; D016207:Cytokines; D064451:Hepcidins; D008070:Lipopolysaccharides; D011990:Receptors, Transferrin; C480029:Tfrc protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron; D001241:Aspirin
keywords: Aspirin (acetylsalicylic acid, ASA); Ferroportin 1 (Fpn1); Hepcidin; Inflammation and lipopolysaccharides (LPS); Interleukin-6 (IL-6); Iron metabolism; Transferrin receptor 1 (TfR1); Tumor necrosis factor-αlpha (TNF-alpha)