title: Aspirin down Regulates Hepcidin by Inhibiting NF-κB and IL6/JAK2/STAT3 Pathways in BV-2 Microglial Cells Treated with Lipopolysaccharide.
abstract: Aspirin down regulates transferrin receptor 1 (TfR1) and up regulates ferroportin 1 (Fpn1) and ferritin expression in BV-2 microglial cells treated without lipopolysaccharides (LPS), as well as down regulates hepcidin and interleukin 6 (IL-6) in cells treated with LPS. However, the relevant mechanisms are unknown. Here, we investigate the effects of aspirin on expression of hepcidin and iron regulatory protein 1 (IRP1), phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and P65 (nuclear factor-κB), and the production of nitric oxide (NO) in BV-2 microglial cells treated with and without LPS. We demonstrated that aspirin inhibited hepcidin mRNA as well as NO production in cells treated with LPS, but not in cells without LPS, suppresses IL-6, JAK2, STAT3, and P65 (nuclear factor-κB) phosphorylation and has no effect on IRP1 in cells treated with or without LPS. These findings provide evidence that aspirin down regulates hepcidin by inhibiting IL6/JAK2/STAT3 and P65 (nuclear factor-κB) pathways in the cells under inflammatory conditions, and imply that an aspirin-induced reduction in TfR1 and an increase in ferritin are not associated with IRP1 and NO.
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, China. lj19840208@126.com.|Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. lj19840208@126.com.
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Li
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, China. lfm19910916@sina.com.
authors.forename: Fei-Mi
authors.initials: FM
authors.lastname: Li
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, China. zyf19850722@126.com.
authors.forename: Yu-Fu
authors.initials: YF
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. sy19871104@yahoo.com.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Wen
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, China. mj19890412@126.com.|School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. mj19890412@126.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Ma
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. yake@cuhk.edu.hk.
authors.forename: Ke
authors.initials: K
authors.lastname: Ya
authors.affiliation: Laboratory of Neuropharmacology, Fudan University School of Pharmacy, Shanghai 201203, China. qianzhongming@fudan.edu.cn.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Qian
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002460:Cell Line; D064451:Hepcidins / Q000096:biosynthesis* / Q000235:genetics; D007249:Inflammation / Q000473:pathology; D035941:Iron Regulatory Protein 1 / Q000096:biosynthesis; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D001241:Aspirin; D064451:Hepcidins; D035941:Iron Regulatory Protein 1; D053614:Janus Kinase 2; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D051996:Transcription Factor RelA; D000093242:Interleukin-6 Inhibitors; C498144:Rela protein, mouse; C494087:Stat3 protein, mouse; C577686:interleukin-6, mouse; D015850:Interleukin-6; C507926:Jak2 protein, mouse
keywords: IL-6/JAK2/STAT3 pathway; P65 (nuclear factor-κB); aspirin; hepcidin; iron regulatory protein 1 (IRP1); lipopolysaccharide (LPS); nitric oxide (NO)