Beyond anemia: hepcidin, monocytes and inflammation

2013 ◽  
Vol 394 (2) ◽  
pp. 1-10 ◽  
Author(s):  
Xiaolan Zhang ◽  
Brad H. Rovin
Keyword(s):  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Mononuclear Phagocyte ◽  
Hepcidin Expression ◽  
Systemic Level ◽  
Monocytes And Macrophages ◽  
Inflammatory Processes ◽  
Serum Hepcidin ◽  
Relationship Of ◽  
The Relationship

Abstract Hepcidin is an iron regulatory protein mainly synthesized by the liver. Hepatocyte production of hepcidin is responsible for serum hepcidin, is responsive to body iron stores, and is critical for maintaining iron homeostasis. Monocytes and macrophages also express hepcidin, and in contrast to the liver, hepcidin expression is primarily regulated by inflammatory mediators and infectious agents. Monocyte and macrophage hepcidin is likely to be more important on a local rather than systemic level, contributes to host defense and may modulate inflammatory processes. This review summarizes recent findings and hypotheses on the relationship of hepcidin to the mononuclear phagocyte system.

Beyond anemia: hepcidin, monocytes and inflammation

2013 ◽  
Vol 394 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Xiaolan Zhang ◽  
Brad H. Rovin
Keyword(s):  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Mononuclear Phagocyte ◽  
Hepcidin Expression ◽  
Systemic Level ◽  
Monocytes And Macrophages ◽  
Inflammatory Processes ◽  
Serum Hepcidin ◽  
Relationship Of ◽  
The Relationship

Abstract Hepcidin is an iron regulatory protein mainly synthesized by the liver. Hepatocyte production of hepcidin is responsible for serum hepcidin, is responsive to body iron stores, and is critical for maintaining iron homeostasis. Monocytes and macrophages also express hepcidin, and in contrast to the liver, hepcidin expression is primarily regulated by inflammatory mediators and infectious agents. Monocyte and macrophage hepcidin is likely to be more important on a local rather than systemic level, contributes to host defense and may modulate inflammatory processes. This review summarizes recent findings and hypotheses on the relationship of hepcidin to the mononuclear phagocyte system.

scholarly journals Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Lucien McBeth ◽  
Maria Grabnar ◽  
Steven Selman ◽  
Terry D. Hinds
Keyword(s):  
Bladder Cancer ◽  
Glucocorticoid Receptors ◽  
Lifestyle Risk Factors ◽  
Glucocorticoid Signaling ◽  
Major Player ◽  
Inflammatory Processes ◽  
Lifestyle Risk ◽  
Relationship Of ◽  
The Relationship ◽  
Male To Female

Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-)αisoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer.

scholarly journals Chuvash polycythemia VHLR200W mutation is associated with down-regulation of hepcidin expression

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5278-5282 ◽  
Author(s):  
Victor R. Gordeuk ◽  
Galina Y. Miasnikova ◽  
Adelina I. Sergueeva ◽  
Xiaomei Niu ◽  
Mehdi Nouraie ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Cell Mass ◽  
Hypoxia Inducible Factor ◽  
Loss Of Function ◽  
Ferritin Concentration ◽  
Hepcidin Expression ◽  
Serum Ferritin Concentration ◽  
Serum Hepcidin ◽  
Relationship Of ◽  
Serum Erythropoietin

Abstract Hypoxia is known to reduce the expression of hepcidin, the master regulator of iron metabolism. However, it is not clear whether this response is primarily related to increased erythropoiesis driven by hypoxically stimulated erythropoietin or to a more direct effect of hypoxia on hepcidin expression. The germline loss-of-function VHLR200W mutation is common in Chuvashia, Russia, and also occurs elsewhere. VHLR200W homozygotes have elevated hypoxia-inducible factor 1α (HIF-1α) and HIF-2α levels, increased red cell mass, propensity to thrombosis, and early mortality. Ninety VHLR200W homozygotes and 52 controls with normal VHL alleles from Chuvashia, Russia, were studied under basal circumstances. In univariate analyses, serum hepcidin concentration was correlated positively with serum ferritin concentration and negatively with homozygosity for VHLR200W. After adjustment for serum erythropoietin and ferritin concentrations by multiple linear regression, the geometric mean (95% confidence interval of mean) hepcidin concentration was 8.1 (6.3-10.5) ng/mL in VHLR200W homozygotes versus 26.9 (18.6-38.0) ng/mL in controls (P < .001). In contrast, a significant independent relationship of serum erythropoietin, hemoglobin, or RBC count with hepcidin was not observed. In conclusion, up-regulation of the hypoxic response leads to decreased expression of hepcidin that may be independent of increased erythropoietin levels and increased RBC counts.

Hepcidin inhibition improves iron homeostasis in ferrous sulfate and LPS treatment model in mice

Drug Research ◽  
2021 ◽  
Author(s):  
Vishal Patel ◽  
Amit Joharapurkar ◽  
Samadhan Kshirsagar ◽  
Maulik Patel ◽  
Hiren Patel ◽  
...  
Keyword(s):  
Ferrous Sulfate ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
The Body ◽  
Rapid Screening ◽  
Iron Dextran ◽  
Liver Iron ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Lps Treatment

Abstract Background Hepcidin, a liver-derived peptide, regulates the absorption, distribution, and circulation of iron in the body. Inflammation or iron overload stimulates hepcidin release, which causes the accumulation of iron in tissues. The inadequate levels of iron in circulation impair erythropoiesis. Inhibition of hepcidin may increase iron in circulation and improve efficient erythropoiesis. Activin-like kinase (ALK) inhibitors decrease hepcidin. Methods In this work, we have investigated an ALK inhibitor LDN193189 for its efficacy in iron homeostasis. The effect of LDN193189 treatment was assessed in C57BL6/J mice, in which hepcidin was induced by either ferrous sulfate or lipopolysaccharide (LPS) injection. Results After two hours of treatment, ferrous sulfate increased serum and liver iron, serum hepcidin, and liver hepcidin expression. On the other hand, LPS reduced serum iron in a dose-related manner after six hours of treatment. LDN193189 treatment increased serum iron, decreased spleen and liver iron, decreased serum hepcidin and liver hepcidin expression in ferrous sulfate-treated mice, and increased serum iron in LPS-induced hypoferremia. We observed that ferrous sulfate caused a significantly higher increase in liver iron, serum hepcidin, and liver hepcidin than turpentine oil or LPS in mice. Iron dextran (intraperitoneal or intravenous) increased serum iron, but LDN193189 did not show hyperferremia with iron dextran stimulus. Conclusion Ferrous sulfate-induced hyperferremia can be a valuable and rapid screening model for assessing the efficacy of hepcidin inhibitors.

Inflammatory diseases of the pelvic organisms modern presentations about etiology, principles of diagnosis and treatment

2020 ◽  
pp. 7-14
Author(s):  
N.M. Hychka ◽  
◽  
O.A. Shcherba ◽  
L.D. Lastovetska ◽  
◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Reproductive Organs ◽  
Pelvic Peritoneum ◽  
Inflammatory Processes ◽  
Diagnostic Approaches ◽  
Principles Of Treatment ◽  
Relationship Of ◽  
The Relationship

Inflammatory diseases of the pelvic organs (PID) occupy the first place in the structure of gynecological morbidity and are one of the causes of dysfunction of not only the reproductive organs but also various systems of the female body, infertility, and a decrease in the quality of life. The PID includes inflammatory processes of the uterus, fallopian tubes, ovaries and pelvic peritoneum. The article presents modern views on etiological factors, stages of development of endogenous infection and its clinical manifestations. The mechanisms of endocrine and immune regulation of the vaginal microbiocenosis, as well as the relationship of endogenous microflora and pathogens of exogenous genital infections, are examined. Diagnostic approaches and principles of treatment of PID are presented, taking into account the severity of the infectious process. Key words: рelvic inflammatory diseases, salpingitis, endometritis, microbiocenosis, sexual exinfection, diagnosis, treatment principles.

scholarly journals Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 630-637 ◽  
Author(s):  
Thomas B. Bartnikas ◽  
Nancy C. Andrews ◽  
Mark D. Fleming
Keyword(s):  
Microcytic Anemia ◽  
Iron Availability ◽  
Hepcidin Expression ◽  
Tissue Iron ◽  
And Control ◽  
Relationship Of ◽  
The Relationship ◽  
Deficient Mice

AbstractAs a central regulator of iron metabolism, hepcidin inhibits dietary iron absorption and macrophage iron recycling. Its expression is regulated by multiple factors including iron availability and erythropoietic activity. To investigate the role of transferrin (Tf) in the regulation of hepcidin expression by these factors in vivo, we employed the hypotransferrinemic (hpx) mouse. These Tf-deficient mice have severe microcytic anemia, tissue iron overload, and hepcidin deficiency. To determine the relationship of Tf levels and erythropoiesis to hepcidin expression, we subjected hpx mutant and control mice to a number of experimental manipulations. Treatment of hpx mice with Tf injections corrected their anemia and restored hepcidin expression. To investigate the effect of erythropoiesis on hepcidin expression, we suppressed erythropoiesis with blood transfusions or myeloablation with chemotherapeutic drugs. Transfusion of hpx animals with wild-type red blood cells led to increased hepcidin expression, while hepcidin expression in myeloablated hpx mice increased only if Tf was administered postablation. These results suggest that hepcidin expression in hpx mice is regulated both by Tf-restricted erythropoiesis and by Tf through a mechanism independent of its role in erythropoiesis.

Analysis Of The Molecular Mechanisms Leading To Significantly Higher Serum Hepcidin and More Severe Anemia In Multicentric Castleman’s Disease (MCD) Patients Than In Rheumatoid Arthritis (RA) Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2181-2181
Author(s):  
Soken-Nakazawa J. Song ◽  
Hiroshi Kawabata ◽  
Kazuyuki Yoshizaki
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Severe Anemia ◽  
Negative Regulators ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
The Mean

Abstract Background Hepcidin is a key regulator of body iron homeostasis and its increase in synthesis is implicated in anemia of inflammation (AI), which is commonly observed in patients with chronic inflammatory disorders such as MCD and RA. Inflammatory cytokines, mainly interleukin-6 (IL-6), play a central role in hepcidin induction during inflammation. However, tumor necrosis factor-a (TNF-a) does not induce but rather inhibits hepcidin expression in vitro and in vivo. The bone morphogenetic proteins (BMP) and erythropoietin (EPO) are the known positive and negative regulators of hepcidin expression. Our preliminary data has showed that MCD patients have more severe anemia and higher serum hepcidin-25 concentration than did RA patients. To clarify the mechanisms resulting in this difference, the activated patterns of hepcidin-regulating cytokines and their associations with serum hepcidin-25 levels and severity of anemia were analyzed in MCD and RA patients. Methods 42 patients with AI (14 with MCD and 28 with RA) treated with tocilizumab (an anti-IL-6 receptor antibody) were enrolled in this study. Major iron-related parameters including serum hepcidin-25, and serum levels of cytokines including IL-6, TNF-a, BMP and EPO were measured and correlations with hepcidin-25 as well as Hb were evaluated. Effects of cytokines on IL-6-induced hepcidin expression were analyzed in hepatoma cells by quantitative real-time PCR. Results The mean levels of hepcidin-25 at baseline was significantly higher (44.6 ng/ml), and Hb was significantly lower (9.2 g/dL) in MCD, than those in RA (28.6 ng/ml for hepcidin-25, 11.2 g/dL for Hb). There were significant and positive correlations of serum hepcidin-25 levels with serum ferritin and CRP in both groups (r=0.67 and 0.68 for ferritin, and r=0.41 and 0.36 for CRP, p< 0.001 respectively for both). In contrast, serum hepcidin-25 levels did not show any significant correlation with the levels of serum IL-6 or BMP or TNF-a (p > 0.05, respectively for both groups). The mean values of IL-6, TNF-a, BMP2, BMP4 and hepcidin-25 at baseline were elevated in two groups as compared to healthy control. Of note, we found that MCD patients showed significantly lower serum TNF-a (mean 195 pg/ml) and higher serum BMP4 (mean 193 pg/ml) concentrations than did RA patients (TNF-a= 241 pg/ml, BMP4= 92 pg/ml), although the two patient groups showed comparably elevated values for IL-6, BMP2 and EPO (p> 0.05, respectively). Significant improvements in anemia and systemic symptoms, and reductions in serum hepcidin-25 levels were observed within 2 weeks in both groups after tocilizumab treatment. In in vitro experiments, IL-6-induced hepcidin mRNA expression in hepatocytes was completely inhibited with tocilizumab and partially with TNF-a, but enhanced by BMP4 as well as MCD patient's serum. These results suggest that the negative effect of TNF-a on the IL-6-induced hepcidin was more pronounced in the RA than in MCD, in contrast, the positive effect of BMP was stronger in MCD than in RA. In addition, the finding that IL-6-induced hepcidin in hepatocytes was enhanced only by adding MCD patients’ serum but not RA patients’ serum, indicating the activated pattern of serum hepcidin-regulating factors in the MCD different from it in RA. Conclusions Our results suggest that the difference between MCD and RA in serum hepcidin-25 levels is partially due to the different activated patterns of positive and negative regulators of hepcidin expression. By the evidence that treatment with tocilizumab can reduce serum hepcidin and improve AI in patients with MCD and RA, we believe that IL-6 plays an essential role in the induction of hepcidin which leads to AI in MCD and RA, although multiple factors affect hepcidin levels. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association of Serum Hepcidin Levels with Aerobic and Resistance Exercise: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 393
Author(s):  
Phureephat Larsuphrom ◽  
Gladys Oluyemisi Latunde-Dada
Keyword(s):  
Oxygen Delivery ◽  
Iron Homeostasis ◽  
Cochrane Library ◽  
Post Exercise ◽  
Hepcidin Expression ◽  
Before And After ◽  
Serum Hepcidin ◽  
Exercise Programmes ◽  
Exercise Induced ◽  
Response To Exercise

Background: Prevalence of iron deficiency is commonly reported among athletic population groups. It impairs physical performance due to insufficient oxygen delivery to target organs and low energy production. This is due to the high demand of exercise on oxygen delivery for systemic metabolism by the erythrocytes in the blood. Hepcidin, the key regulator of iron homeostasis, decreases to facilitate iron efflux into the circulation during enhanced erythropoiesis. However, acute anaemia of exercise is caused by increased hepcidin expression that is induced by stress and inflammatory signal. The study aimed to systematically review changes in serum hepcidin levels during resistance and aerobic exercise programmes. Methods: A systemic literature search from 2010 to April 2020 across seven databases comprised of Cochrane library, PubMed, Web of Science, Scopus, Embase, MEDLINE, and OpenGrey. The primary outcome was increased or decreased serum hepcidin from baseline after the exercise activity. Risks of bias were evaluated by using the National Institutes of Health (NIH) for quality assessment of before and after different exercise programmes. Results: Overall, twenty-three studies met the inclusion criteria. Out of the 23 studies, 16 studies reported significantly exercise-induced serum hepcidin elevation. Of the 17 studies that evaluated serum interleukin (IL)-6 levels, 14 studies showed significant exercise-induced serum IL-6 elevation. Changes in exercise-induced serum hepcidin and IL-6 levels were similar in both resistance and endurance exercise. Significant correlations were observed between post-exercise hepcidin and baseline ferritin levels (r = 0.69, p < 0.05) and between post-exercise hepcidin and post-exercise IL-6 (r = 0.625, p < 0.05). Conclusion: Resistance and endurance training showed significant increase in serum hepcidin and IL-6 levels in response to exercise. Baseline ferritin and post-exercise IL-6 elevation are key determining factors in the augmentation of hepcidin response to exercise.

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