Iron in joint inflammation.

Dabbagh, Alya; Trenam, Charles W.; Morris, C J; Blake, David R.

doi:10.1136/ard.52.1.67

Cited by 55 publications

(32 citation statements)

References 63 publications

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“…Each of these forms might be able to release iron to form hydroxyl radicals 212 Moreover, iron exists in the form of citrate as non-transferrin bound iron, one of the low molecular weight chelators in RA synovia, being a donor for iron in the Haber-Weiss reaction 2. Interestingly, it was recently demonstrated that K562 cells, an erythroid leukaemia cell line, have two iron transport systems: (1) the classic transferrin (Tf) mediated iron uptake via the Tf receptors, and (2) a non-Tf (commonly citrate) pathway via cell surface integrin 13.…”

Section: Discussionmentioning

confidence: 99%

“…Since Muirden and Senator reported the deposition of iron in synovial tissue in rheumatoid arthritis (RA) patients,1the roles of iron in joint inflammation have been discussed extensively 2. For example, iron catalyses oxidative radical reactions (Haber-Weiss reaction), which lead to the formation of the most toxic hydroxyl radical and subsequent lipid peroxidation and tissue damage 2.…”

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confidence: 99%

“…For example, iron catalyses oxidative radical reactions (Haber-Weiss reaction), which lead to the formation of the most toxic hydroxyl radical and subsequent lipid peroxidation and tissue damage 2. Iron also changes the lymphocyte migration to the joint and modulates T cell surface molecule expression,3 macrophage phagocytic function,4and natural killer cell activity 5.…”

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confidence: 99%

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Down regulation by iron of prostaglandin E2 production by human synovial fibroblasts

Hisakawa¹,

Nishiya²,

Tahara³

et al. 1998

Annals of the Rheumatic Diseases

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Objective-To examine the eVect of iron on the prostaglandin (PG) E 2 production by human synovial fibroblasts in vitro. Methods-Human synovial fibroblasts were isolated from synovial tissue of rheumatoid arthritis (RA) and osteoarthritis (OA) patients and cultured in medium. Synovial fibroblasts were stimulated by human recombinant interleukin (IL) 1 (0.1-10 ng/ml) with or without ferric citrate (Fe-citrate, 0.01-1 mM). The amount of PGE 2 in the culture medium was measured by an enzyme linked immunosorbent assay. Results-The production of PGE 2 by the synovial fibroblasts was increased by stimulation with IL1 at all concentrations tested. Fe-citrate but not sodium citrate (Na-citrate) down regulated the production of PGE 2 by the synovial fibroblasts, both with and without stimulation by IL1 . Fe-citrate inhibited the spontaneous PGE 2 production by the cells in a dose dependent manner, and a maximum inhibition by Fe-citrate was observed at the concentration of 0.1 mM with IL1 stimulation. The down regulation by iron was reversed by the co-addition of desferrioxamine (100 µg/ml), an iron chelator. Conclusion-Iron down regulates the PGE 2 production by synovial fibroblasts in vitro.

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Section: Discussionmentioning

confidence: 99%

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Down regulation by iron of prostaglandin E2 production by human synovial fibroblasts

Hisakawa¹,

Nishiya²,

Tahara³

et al. 1998

Annals of the Rheumatic Diseases

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“…Epidemiologic studies have shown an inverse association between dietary intake of antioxidants and RA incidence [14-17], and inverse associations between antioxidant levels and inflammation have been found [18,19]. Iron, a catalyst for hydroxyl radical production from hydrogen peroxide (see Table 1), is present in RA synovial tissue and is associated with poorer prognosis [20]. Several groups have demonstrated increased oxidative enzyme activity along with decreased antioxidant levels in RA sera and synovial fluids [21-25].…”

Section: Evidence For Oxidative Stress In Ramentioning

confidence: 99%

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2004

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265 AGE = advanced glycation endproducts; HIF-1α = hypoxia-inducible factor-1α; LDL = low-density-lipid proteins; MAP = mitogen-activated protein; MMR = mismatch repair; mtDNA = mitochondrial DNA; NF-κB = nuclear factor-κB; PHD = prolyl hydroxylase; PI-3K = phosphoinositide 3-kinase; RA = rheumatoid arthritis; RNS = reactive nitrogen species; ROS = reactive oxygen species; SOD = superoxide dismutase; TGF = transforming growth factor; TNF = tumor necrosis factor; VEGF = vascular endothelial growth factor; VHL = von Hippel-Landau tumor suppressor factor. Available online http://arthritis-research.com/content/6/6/265 Introduction Molecular oxygen is essential for the survival of all aerobic organisms. Aerobic energy generation is dependent on oxidative phosphorylation, a process by which the oxidoreduction energy of mitochondrial electron transport is converted to the high-energy phosphate bond of ATP. In this multi-step enzymatic process, oxygen serves as the final electron acceptor for cytochrome c oxidase, the terminal component of the mitochondrial enzymatic complex that catalyzes the four-electron reduction of O 2 to H 2 O. A byproduct of this process is the production of partly reduced oxygen metabolites that are highly reactive and that leak out of the mitochondria and react rapidly with other molecules. In turn, reactive nitrogen species, sulfur-centered radicals, and other reactive species are generated by interactions with these molecules. Reactive oxygen species (ROS) participate in several physiological functions, and form an integral part of the organism's defense against invading microbial agents.Because of their potentially damaging effects, several antioxidant mechanisms have evolved to protect cells and organisms from damage by excessive amounts of these highly reactive mediators. Oxidative stress is a term that is used to describe situations in which the organism's production of oxidants exceeds the capacity to neutralize them. The result can be damage to cell membranes, lipids, nucleic acids, proteins, and constituents of the extracellular matrix such as proteoglycans and collagens.Extended periods of hypoxia, or brief periods of complete anoxia, invariably lead to death. In contrast, cellular hypoxia occurs frequently, both physiologically and pathologically, and serves as a potent stimulus for changes in gene transcription, translation, and several post-translational protein modifications that serve to rapidly adapt cells and tissues to this stimulus. Oxygen levels vary considerably in different tissues -and even in different areas of a single tissue -and depend on a complex interaction of Review Oxidation in rheumatoid arthritis AbstractOxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. Reactive oxygen species (ROS) produced in the course of cellular oxidative phosphorylation, and by activated phagocytic cells during oxidative bursts, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein...

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“…MOUITHYS-MICKALAD et al infiltrated and resident cells [1][2][3][4][5][6]. Furthermore, some NSAIDs have been demonstrated to be potent scavengers of reactive oxygen species (ROS) and inhibitors of the intracellular oxidase activity [7][8][9][10][11][12][13][14][15][16]. Since we know that ROS produced in excess at the inflammatory site play key roles in the progression of the rheumatoid inflammation, they constitute potential targets for drugs used in rheumatoid arthritis (RA) treatment.…”

Section: Introductionmentioning

confidence: 99%