Regulatory effects of tumor necrosis factor-alpha and interleukin-6 on HAMP expression in iron loaded rat hepatocytes

Dzikaite, Vijole; Holmström, Petra; Stål, Per; Eckes, Kristina; Hagen, Karin; Eggertsen, Gösta; Gåfvels, Mats; Melefors, Öjar; Hultcrantz, Rolf

doi:10.1016/j.jhep.2005.07.028

Cited by 18 publications

(12 citation statements)

References 42 publications

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“…The relationships between TNF-α and the expression of FPN1 mRNA in rat [37] and mouse hepatocytes [36] and human monocytic cells have been confirmed in other studies [38]. We have also demonstrated TNF-α-induced iron sequestration in human umbilical vein endothelial cells, and iron accumulation in polymorphonuclear cells from the patients on MHD whose levels of IL-6 and TNF-α were higher than those of healthy volunteers.…”

Section: Cytokines and Expression Of Ferritin Proteinsupporting

confidence: 82%

“…From the observations that (1) H-ferritin gene transcription is predominantly active in inflammatory conditions, whereas L-ferritin is induced only after exposure to very high iron concentrations and is preferentially secreted to plasma from hepatocytes; (2) the expression of both types of ferritin proteins are exclusively dependent on intracellular free iron which is often sequestered by LPS, TNF-α, or hepcidin in several cell types including hepatocytes [37], reticuloendothelial cells [38], human umbilical vein endothelial cells [39], and polymorphonuclear cells [40], and (3) in conditions of both inflammation and iron deficiency, splenic iron is depleted and serum ferritin does not increase, we may presume that elevated serum ferritin levels could be closely associated with a higher storage of iron while cytokines or inflammation might modulate the ratio of ferritin to body iron storage (fig. 5).…”

Section: Serum Ferritin Reflects Iron Storagementioning

confidence: 99%

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Importance of Ferritin for Optimizing Anemia Therapy in Chronic Kidney Disease

et al. 2010

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The clinical significance of serum ferritin in monitoring the iron status of patients on maintenance hemodialysis (MHD) has become suspected. In this review, we reassess the interpretation of high serum ferritin values in such patients, with the goal of treating their anemia in a safe way. From the observations that (1) H-ferritin gene transcription is predominantly active in inflammatory conditions, whereas L-ferritin is induced only after exposure to very high iron concentrations and is preferentially secreted to plasma from hepatocytes; (2) the expression of both types of ferritin proteins are exclusively dependent on intracellular free iron, which is often sequestered by LPS or cytokines in several cell types, and (3) splenic iron is depleted and serum ferritin does not increase in the combined conditions of both inflammation and iron deficiency, it is deduced that elevated serum ferritin levels are caused by the accumulation of intracellular iron, especially reticuloendothelial cells or macrophages, hepatocytes, and other cells, while cytokines or inflammation might modulate the relative ratio of ferritin to body iron storage. Therefore, high levels of serum ferritin in patients on MHD can be used to indicate iron deposition in most cells, including vascular and immunocompetent cells, and is still a reliable indicator of the need to withhold iron administration.

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Section: Cytokines and Expression Of Ferritin Proteinsupporting

confidence: 82%

Section: Serum Ferritin Reflects Iron Storagementioning

confidence: 99%

Importance of Ferritin for Optimizing Anemia Therapy in Chronic Kidney Disease

et al. 2010

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“…However, pathways for NTBI uptake are less clearly defined compared to TBI uptake. In addition, several previous studies with NTBI showed no effect [1,24] or even down regulation [15,25,27] of hepcidin mRNA. Moreover, the holo-Tf treatment medium was prepared in serum-free Eagle's Minimal Essential Medium (EMEM) that is deprived of inorganic iron sources.…”

Section: Discussionmentioning

confidence: 89%

Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells

Mehta

Greenwell

Renshaw

et al. 2015

Blood Cells, Molecules, and Diseases

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Iron overload coupled with low hepcidin levels are characteristics of hereditary haemochromatosis. To understand the role of transferrin receptor (TFR) and intracellular iron in hepcidin secretion Chinese hamster ovary transferrin receptor variant (CHO TRVb-1) cells were used that express iron-response-element-depleted human TFRC mRNA (TFRC∆IRE).Results showed that CHO TRVb-1 cells expressed higher basal levels of cell-surface TFR1 than HepG2 cells (2.2-fold; p<0.01) and following 5 g/L holotransferrin treatment maintained constitutive over-expression at 24 h and 48 h, contrasting the HepG2 cells where the receptor levels significantly declined. Despite this, the intracellular iron content was neither higher than HepG2 cells nor increased over time under basal or holotransferrin-treated conditions. Interestingly, hepcidin secretion in CHO TRVb-1 cells exceeded basal levels at all timepoints (p<0.02) and matched levels in HepG2 cells following treatment. While TFRC mRNA expression showed expected elevation (2 h, p<0.03; 4 h; p<0.05), slc40a1 mRNA expression was also elevated (2 h, p<0.05; 4 h, p<0.03), unlike the HepG2 cells. In conclusion, the CHO TRVb-1 cells prevented cellular iron-overload by elevating slc40a1 expression, thereby highlighting its significance in the absence of iron-regulated TFRC mRNA. Furthermore, hepcidin response to holotransferrin treatment was similar to HepG2 cells and resembled the human response.

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“…Hepcidin was initially identified as liver-derived antimicrobial peptide (LEAP-1) (69, 109, 116) and immediately uncovered as a major product released in response to inflammatory cytokines, in particular interleukin-6 (IL-6) (32, 96, 98, 101). The peptide is also produced by cells of the immune system (e.g., macrophages and neutrophils) during the innate immune response through a toll-like receptor-4 (TLR-4) dependent pathway (112, 140, 144).…”

Section: Hepcidinmentioning

confidence: 99%

Iron Homeostasis and the Inflammatory Response

2010

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Iron and its homeostasis are intimately tied to the inflammatory response. The adaptation to iron deficiency, which confers resistance to infection and improves the inflammatory condition, underlies what is probably the most obvious link: the anemia of inflammation or chronic disease. A large number of stimulatory inputs must be integrated to tightly control iron homeostasis during the inflammatory response. In order to understand the pathways of iron trafficking and how they are regulated, this chapter will present a brief overview of iron homeostasis. A major focus will be on the regulation of the peptide hormone hepcidin during the inflammatory response and how its function contributes to the process of iron withdrawal. The review will also summarize new and emerging information about other iron metabolic regulators and effectors that contribute to the inflammatory response. Potential benefits of treatment to ameliorate the hypoferremic condition promoted by inflammation will also be considered.

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Regulatory effects of tumor necrosis factor-alpha and interleukin-6 on HAMP expression in iron loaded rat hepatocytes

Cited by 18 publications

References 42 publications

Importance of Ferritin for Optimizing Anemia Therapy in Chronic Kidney Disease

Importance of Ferritin for Optimizing Anemia Therapy in Chronic Kidney Disease

Characterisation of hepcidin response to holotransferrin treatment in CHO TRVb-1 cells

Iron Homeostasis and the Inflammatory Response

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