STAT3 Is Required for IL-6-gp130–Dependent Activation of Hepcidin In Vivo

Pietrangelo, Antonello; Dierssen, U.; Valli, Linda; Garuti, Cinzia; Rump, Agrani; Corradini, Elena; Ernst, Matthias; Klein, Christian; Trautwein, Christian

doi:10.1053/j.gastro.2006.10.018

Cited by 285 publications

(184 citation statements)

References 40 publications

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“…17,[27][28][29][30] Most of these cytokines are known secreted products of macrophages and monocytes. Our data revealed a substantial induction of both IL-6 and IL-1β mRNA in THP1 cells following activation with PMA.…”

Section: Discussionmentioning

confidence: 99%

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells

Matak¹,

Chaston²,

Chung³

et al. 2009

Haematologica

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BackgroundHepcidin is an iron regulatory peptide produced by the liver in response to inflammation and elevated systemic iron. Recent studies suggest that circulating monocytes and resident liver macrophages -Küpffer cells -may influence both basal and inflammatory expression of hepcidin. Design and MethodsWe used an in vitro co-culture model to investigate hepatocyte hepcidin regulation in the presence of activated THP1 macrophages. HuH7 hepatoma cells were co-cultured with differentiated THP1 macrophages for 24 h prior to the measurement of HuH7 hepcidin (HAMP) mRNA expression using quantitative polymerase chain reaction, and HAMP promoter activity using a luciferase reporter assay. Luciferase assays were performed using the wild type HAMP promoter, and constructs containing mutations in BMP/SMAD4, STAT3, C/EBP and E-BOX response elements. Neutralizing antibodies against interleukin-6, interleukin-1β, and the bone morphogenetic protein inhibitor noggin were used to identify the macrophage-derived cytokines involved in the regulation of HAMP expression. ResultsCo-culturing HuH7 cells with differentiated THP1 cells induced HAMP promoter activity and endogenous HAMP mRNA expression maximally after 24 h. This induction was fully neutralized in the presence of an interleukin-1β antibody, and fully attenuated by mutations of the proximal C/EBP or BMP/SMAD4 response elements. ConclusionsOur data suggest that the interleukin-1β and bone morphogenetic protein signaling pathways are central to the regulation of HAMP expression by macrophages in this co-culture model.Key words: hepcidin; hepatocytes, macrophages, cytokines, inflammation. HuH7 hepatoma cells. Haematologica 2009; 94:773-780. doi:10.3324/haematol.2008 This is an open-access paper. Citation: Matak P, Chaston TB, Chung B, Srai SK, McKie AT, and Sharp PA. Activated macrophages induce hepcidin expression in Activated macrophages induce hepcidin expression in HuH7 hepatoma cells

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Section: Discussionmentioning

confidence: 99%

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells

Matak¹,

Chaston²,

Chung³

et al. 2009

Haematologica

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“…7 This study underlines the Iron regulation during acute-phase reaction N Sheikh et al differences between the two animal models and indirectly confirms that IL-6 is the major player in modifying iron metabolism under acute-phase condition. 13,[38][39][40][41][42][43][44] Most studies to date have shown that the transcriptional changes in the Hepc gene expression parallel the changes in serum iron concentration; however, limited studies have been performed to show the changes in the concentration of this important hormone in the serum. [45][46][47][48] Intramuscular TO injection induced significant decrease of the serum iron concentration without a significant change in serum proHepc concentration.…”

Section: Discussionmentioning

confidence: 99%

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

Sheikh

Dudás

Ramadori

2007

Laboratory Investigation

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“…Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality [6,7,[11][12][13][14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

The effect of ursodeoxycholic acid on Messenger RNA hepcidin expression associated with liver fibrosis in perposed cholestasis jaundice

S¹,

Y²

2017

clinical-practice

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Objectives: Cholestasis in extra hepatic obstruction induce cells stress and associated with the induction of inflammatory that correlate with hepcidin Messenger RNA (mRNA) expression. In our research we tried to analize the correlation between induced chlolestatis with MRNA expression of hepcidin.Methods : By using the 24 of Wistar rats -male with an average weight of standard 240 g, 200 g, were divided into 2 groups; artificial cholestasis without intervention and Artificial cholestasis with intervention of ursodeoxycholic acid. We use total RNA isolation from rat liver tissue by using GeneJet RNA Purification Kit (Thermo Sciencetific).Results : RNA levels were measured using a TECAN Infinate 200 NanoQuant. Hepcidin mRNA expression was measured by real-time Quantitive recieve transcription PCR LightCycler.Conclusion : MRNA expression of hepcidin decreased significantly ( p<0.01) in the ursodeoxycholic acid group. Increased Plasma hepcidin is proven associated with progression of liver fibrosis and correlated with prognosis.

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STAT3 Is Required for IL-6-gp130–Dependent Activation of Hepcidin In Vivo

Cited by 285 publications

References 40 publications

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells

Activated macrophages induce hepcidin expression in HuH7 hepatoma cells

Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat

The effect of ursodeoxycholic acid on Messenger RNA hepcidin expression associated with liver fibrosis in perposed cholestasis jaundice

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