title: Interferon-gamma induced nitric oxide-mediated apoptosis of anemia of chronic disease in rheumatoid arthritis.
abstract: Proinflammatory cytokines play a role in the pathogenesis of anemia of chronic disease (ACD), which is a common cause of anemia in rheumatoid arthritis (RA). Anemia in RA is associated with increased apoptosis of erythroid cells. However, there is unclear information on the mechanism of ACD in the disease. The purpose of this study is to investigate the role of cytokines on nitric oxide-mediated apoptosis in erythroid progenitor cells of ACD in RA patients. Erythroid progenitor cells from healthy subjects and RA patients with ACD were treated with cytokines like interleukin-1β, tumor necrosis factor-α, and interferon-γ at concentrations of 2, 20, and 40 ng/ml for 14 days. Cell viability and cell apoptosis were analyzed by trypan blue staining and flow cytometry, respectively. The results showed that the highest effect of cytokines on reduction cell viability and induction cell apoptosis was found in 20 ng/ml IFN-γ-treated cells of RA patients. In addition, IFN-γ showed significantly increased nitric oxide production and iNOS mRNA expression, which was measured by Griess assay and real-time PCR, respectively. The percentage of cell apoptosis and NO production was reduced after an inducible nitric oxide synthase inhibitor, SMT, treatment. In conclusion, IFN-γ could induce nitric oxide production-mediated apoptosis process, which might be involved in the pathogenesis of ACD in RA patients.
authors.affiliation: Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, 999 Phutthamonthon 4 Road Salaya, Phutthamonthon 4, Nakhonpathom 73170, Thailand.
authors.forename: Wasinee
authors.initials: W
authors.lastname: Kheansaard
authors.forename: Sumana
authors.initials: S
authors.lastname: Mas-Oo-di
authors.forename: Surasak
authors.initials: S
authors.lastname: Nilganuwong
authors.forename: Dalina I
authors.initials: DI
authors.lastname: Tanyong
mesh_terms: D000740:Anemia / Q000097:blood / Q000209:etiology*; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000378:metabolism; D005293:Ferritins / Q000097:blood; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007501:Iron / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D005293:Ferritins; D007501:Iron; D052247:Nitric Oxide Synthase Type II