Iron Homeostasis and the Inflammatory Response

Wessling‐Resnick, Marianne

doi:10.1146/annurev.nutr.012809.104804

Cited by 389 publications

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“…23 However, in Steap3 -/-mice treated with LPS, serum iron concentrations, total iron-binding capacity and transferrin saturation only showed a marginally decreasing trend (P=0.08) at 6 h after LPS treatment ( Figure 4A-4D).…”

Section: Steap3 -/-Mice Following Lipopolysaccharide Stimulationmentioning

confidence: 90%

Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundIron and its homeostasis are intimately related to inflammatory responses, but the underlying molecular mechanisms are poorly understood. We investigated the role of Steap3 in regulating iron homeostasis in macrophages, and the effects of Steap3 depletion on host inflammatory responses. Design and MethodsWe analyzed bone marrow-derived macrophages and primary cultured hepatocytes from Steap3 -/-mouse models to investigate the roles of Steap3 in coordinately regulating iron homeostasis and inflammatory responses. First, we examined iron distribution and iron status in cells deficient in Steap3, as well as the requirement for the Steap3 gene during inflammatory responses. Secondly, we analyzed the regulation of Steap3 expression by inflammatory stimuli and thus, the influence of these stimuli on iron distribution and homeostasis. ResultsWe found that Steap3 mRNA was expressed at high levels in macrophages and hepatocytes. Steap3 deficiency led to impaired iron homeostasis, causing abnormal iron distribution and a decreased availability of cytosolic iron in macrophages. Among STEAP family members, Steap3 mRNA was uniquely down-regulated in macrophages stimulated by lipopolysaccharides. To determine whether Steap3 regulated iron homeostasis during inflammatory stress, we treated Steap3 -/-mice with lipopolysaccharide, which produced greater iron accumulation in the vital tissues of these mice compared to in the tissues of wild-type controls. Furthermore, Steap3 depletion led to impaired induction of interferon-b, monocyte chemoattractant protein-5, and interferon induced protein-10 in macrophages via the TLR4-mediated signaling pathway. ConclusionsSteap3 is important in regulating both iron homeostasis and TLR4-mediated inflammatory responses in macrophages. Steap3 deficiency causes abnormal iron status and homeostasis, which leads to impaired TLR4-mediated inflammatory responses in macrophages. Following inflammatory stimuli, Steap3 depletion causes dysregulated iron sequestration and distribution. Our results provide important insights into the function of Steap3 as a coordinate regulator of both iron homeostasis and innate immunity. Haematologica 2012;97(12):1826-1835. doi:10.3324/haematol.2012 This is an open-access paper. Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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Section: Steap3 -/-Mice Following Lipopolysaccharide Stimulationmentioning

confidence: 90%

Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses

et al. 2012

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“…In our patient deviation from diet rules resulted in a peak in inflammation associated with iron deficiency anaemia. Importantly, low iron and high CRP are both regarded as negative predictors of colorectal cancer outcome [31,32]. Low iron, in addition, has been suggested to form part of the inflammatory response [33].…”

Section: Discussionmentioning

confidence: 99%

“…Pulse was relatively stable and low (mean±SD: 56.8±3.9 beat/min; Figure 2D). 31 Jan 2017 showed a marked elevation in all three inflammatory markers (CRP, fibrinogen and ESR) along with decreased iron level. The patient was then started on the strictest version of the paleolithic ketogenic diet, the full meat-fat diet.…”

Section: Home Monitoring Of Parametersmentioning

confidence: 99%

Treatment of Rectal Cancer with the Paleolithic Ketogenic Diet: A 24-months Follow-up

Tóth¹,

Clemens²

2017

AJMCR

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Background: Ketogenic diets have repeatedly been suggested for the treatment of cancer. Yet, only a few case studies have been published that reported long term benefits associated with such diets. Case report: Here we present a case where rectal cancer was treated with an animal fat-meat based diet, which we refer to as the paleolithic ketogenic diet. Upon diet initiation, the patient discontinued three medicines he had been taking because of hypertension and hyperuricemia. The patient initially received 6 weeks of radiation therapy. Thereafter the patient used the diet as a stand-alone therapy for 22.5 months. The patient was not taking any medicines or dietary supplements while on the diet. During the first five month of the diet therapy the patient exhibited excellent adherence which was paralleled by improving laboratory parameters including decreasing tumor marker levels and decreasing tumor size. The patient was in a constant ketosis during the entire follow-up. From the seventh month on, however, his adherence level was fluctuating with periods of worse adherence paralleled with negative changes in laboratory parameters. Although MRI imaging showed that there was no increase in the size of the tumor, 22 months after diagnosis onset the patient reported an alteration in bowel habits and that the bloody stool had returned. Because of the emergence of these symptoms, 24 months after diagnosis onset, rectal surgery was performed. Conclusion: With using the paleolithic ketogenic diet the patient was able to postpone surgery for two years. During the first five months, when the patient was strictly adhering to the diet, the tumor regressed. Thereafter, with incomplete dietary adherence, disease seemed to be stable but symptoms suggested progression for the last few months of the follow-up. Deviations from diet rules, even those not affecting ketosis, resulted in the progression of the disease.

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“…Entre la primera y la segunda fases hay depleción de los depósitos de hierro y disminución del hierro circulante respectivamente, y en la tercera fase (anemia ferropénica), se afecta la síntesis de hemoglobina. dor para reflejar de forma adecuada el estado del hierro en el organismo, especialmente en casos de anemia por enfermedades crónicas (14,15) e inflamación (16)(17)(18).…”

Section: Introductionunclassified

Hepcidina y parámetros del hierro en donantes de sangre

Murillo-Ramos

Hurtado-Florez²,

Arciniegas-Yampuezán³

et al. 2016

CES Med

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ResumenIntroducción: la hepcidina es la principal hormona peptídica reguladora de la absorción y distribución tisular del hierro. Estudios recientes han planteado la posibilidad de utilizarla como un biomarcador para evaluar el metabolismo del hierro y sus posibles alteraciones. Aunque, ante la escasa información sobre las propiedades diagnósticas de la hepcidina sérica, no han sido bien caracterizadas y no se cuenta con estudios suficientes en individuos sanos, e incluso en Colombia hasta el momento no se ha realizado ningún estudio referente al tema. Objetivo: estimar las concentraciones de la hepcidina sérica, su rango de normalidad y su correlación con parámetros bioquímicos asociados al metabolismo del hierro en una población de donantes. Materiales y métodos: estudio descriptivo transversal que incluyó 85 donantes, a quienes se les realizó hemograma automatizado, se evaluó ferritina, transferrina y hierro total, mediante los mé-todos de electroquimioluminiscencia, inmunoturbidimetría y colorimetría. La determinación de hepcidina en suero se realizó por medio de una ELISA competitiva. Se utilizaron pruebas estadísticas, con un nivel de significancia de p< 0,05. Resultados: se observaron diferencias significativas en la concentración de hepcidina entre hombres y mujeres. La edad no fue un factor determinante de las concentraciones de hepcidina en los hombres Mediana (Me)=5,73 nM. Solo ferritina se correlacionó fuertemente con la hepcidina. El rango de normalidad de hepcidina encontrado en hombres estuvo entre 1,71 y 13,3 nM y entre 1,67 a 11,3 nM en mujeres. Conclusión: el nivel de hepcidina sérica es mayor en hombres y demuestra la fuerte asociación in vivo con los niveles de hepcidina sérica con el hierro de reserva y circulante.Palabras claves: Metabolismo del hierro, Hepcidina, Ferritina , Transferrina, Hierro total. AbstractIntroduction: The hepatic peptide hormone hepcidin is the principal regulator of iron absorption and tissue iron distribution. Recent studies have proposed hepcidin as a suitable biomarker to assess iron metabolism and its failures. Although the data were limited to information on the diagnostic properties of serum hepcidin, have not been well characterized and neither have enough studies in healthy individuals, and even in Colombia so far have not been any studies on the topic. Objective: quantify the concentra-

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Iron Homeostasis and the Inflammatory Response

Cited by 389 publications

References 172 publications

Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses

Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses

Treatment of Rectal Cancer with the Paleolithic Ketogenic Diet: A 24-months Follow-up

Hepcidina y parámetros del hierro en donantes de sangre

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