Pathophysiology of Iron Homeostasis during Inflammatory States

Cherayil, Bobby J.

doi:10.1016/j.jpeds.2015.07.015

Cited by 17 publications

(12 citation statements)

References 57 publications

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“…Moreover, hepcidin expression chronobiologically responded to IL‐6 changes with a drop over time (Figure S7C, Supporting Information), indicating a great correlation between hepcidin induction and IL‐6 stimulation. Due to hepcidin induction, iron egress out of macrophages will be repressed, leading to elevation of iron content in organs 44. As a consequence, we observed increased LICs in all zones from mice 48 h after LPS administration, compared to untreated control, and a greater increase was found in L1‐2 and L1‐3 zones relative to other zones (Figure S7D, Supporting Information), in agreement with the changes of IL‐6 levels.…”

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confidence: 82%

Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders

et al. 2018

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Determination of iron accumulation is crucial in diagnosing the occurrence and progression of many liver‐ and iron‐related diseases. Thus far, little is known about the profiles of iron deposition in different liver zones, particularly under conditions with disordered iron homeostasis. Here, uneven iron distribution in livers of patients with hereditary hemochromatosis (HH) is uncovered, showing the region with the highest iron concentration near the entrance site of the portal vein and hepatic artery in contrast to the sites with the lowest iron concentration close to the distal edge. Distinct iron distribution profiles are also found throughout liver zones in wild‐type mice and various mouse models with iron metabolism disorders, including hemochromatosis (Hfe−/−), iron deficiency, and inflammation. Of note, similar findings observed in HH patients are further demonstrated in Hfe−/− mice. Moreover, the zones with greater iron accumulation appear to be more sensitive to iron changes, e.g., there is iron increase upon iron overload and iron loss in response to iron deficiency. Mechanistic investigation manifests that these differential iron changes in liver zones are subjected to the regulation by the hepcidin–ferroportin axis. Additionally, the data corroborate the reliability of magnetic resonance imaging (MRI) in recognizing the differential iron deposition profiles among liver zones.

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confidence: 82%

Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders

et al. 2018

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“…Our finding that the BMI>35 cohort has a significantly higher RDW and a non-significantly lower MCV is of interest since elevated IL-6 has been shown to promote liver production of the iron-regulatory peptide hormone hepcidin [54,55]. An increase in hepcidin, in turn, is associated with reduced iron uptake from the intestine and increased iron trapping in liver cells and macrophages, thereby reducing iron availability for erythropoiesis [55,56]. This ineffective erythropoiesis may in turn lead to reduced red cell size (i.e., decreased MCV) as well as a greater red cell size distribution (i.e., increased RDW), which is consistent with that found by Vuong et al with their obese participants [57].…”

Section: Blood Cells In the Obese Cohortmentioning

confidence: 83%

Exploratory examination of inflammation state, immune response and blood cell composition in a human obese cohort to identify potential markers predicting cancer risk

et al. 2020

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Obesity has reached epidemic proportions and is often accompanied by elevated levels of pro-inflammatory cytokines that promote many chronic diseases, including cancer. However, not all obese people develop these diseases and it would be very helpful to identify those at high risk early on so that preventative measures can be instituted. We performed an extensive evaluation of the effects of obesity on inflammatory markers, on innate and adaptive immune responses, and on blood cell composition to identify markers that might be useful in distinguishing those at elevated risk of cancer. Plasma samples from 42 volunteers with a BMI>35 had significantly higher CRP, PGE 2 , IL-1RA, IL-6 and IL-17 levels than 34 volunteers with normal BMIs. Of the cytokines and chemokines tested, only IL-17 was significantly higher in men with a BMI>35 than women with a BMI>35. As well, only IL-17 was significantly higher in those with a BMI>35 that had type 2 diabetes versus those without type 2 diabetes. Whole blood samples from participants with a BMI>35, when challenged with E. coli, produced significantly higher levels of IL-1RA while HSV-1 challenge resulted in significantly elevated IL-1RA and VEGF, and a non-significant increase in G-CSF and IL-8 levels. T cell activation of PBMCs, via anti-CD3 plus anti-CD28, resulted in significantly higher IFNγ production from volunteers with a BMI>35. In terms of blood cells, red blood cell distribution width (RDW), monocytes, granulocytes, CD4 + T cells and Tregs were all significantly higher while, natural killer (NK) and CD8 + T cells were all significantly lower in the BMI>35 cohort, suggesting that obesity may reduce the ability to kill nascent tumor cells. Importantly, however, there was considerable person-to-person variation amongst participants with a BMI>35, with some volunteers showing markedly different values from controls and others

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“…It is expressed in cells that absorb (enterocytes) and store (hepatocytes and reticuloendothelial macrophages) iron. Iron that reaches the cytosol is then pumped out, either at the basolateral surface of the enterocyte or the plasma membrane of the macrophage, by FPN [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Any inflammatory conditions are often associated with significant changes in systemic iron metabolism, with altered metabolic state as there is a decrease in plasma iron levels due to reduced intestinal absorption and increased intracellular sequestration of the metal [ 5 ]. T2DM, one of the most prevalent chronic inflammatory diseases worldwide, is associated with cytokine secretion that simultaneously increases transferrin receptors (TfR) on the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

Broide

Reifen

Matalon

et al. 2018

Journal of Diabetes Research

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The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72-1.46), 0.76 (0.53-1.04), and 0.71 (0.64-0.86), respectively (p = 0 011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26-0.61), 0.36 (0.24-0.43), and 0.18 (0.16-0.24), respectively, (p = 0 004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

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Pathophysiology of Iron Homeostasis during Inflammatory States

Cited by 17 publications

References 57 publications

Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders

Distinct Iron Deposition Profiles of Liver Zones in Various Models with Iron Homeostasis Disorders

Exploratory examination of inflammation state, immune response and blood cell composition in a human obese cohort to identify potential markers predicting cancer risk

Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

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