Cytokine-mediated regulation of iron transport in human monocytic cells

In the citing paper

“During infections, pro-inflammatory cytokines play an essential role in hepcidin-independent sequestration of iron. Tumour necrosis factor alpha (TNF-α), interleukins (IL-1 and IL-6), and interferon gamma (IFN-γ) increase uptake of free iron by macrophages and transferrin through upregulation of transferrin receptor proteins (Byrd and Horwitz, 1993; Ludwiczek et al., 2003; Drakesmith and Prentice,”

In the citing paper

“Several of these, including TNF, IL-1, IL-6, IL-10 and IL-22 are known as modifiers of iron homeostasis (Armitage et al., 2011;Ludwiczek et al., 2003;Tilg et al., 2002;Torti and Torti, 2002;Weiss, 2005).”

In the citing paper

“TNF, IFN-γ and IL-10 also stimulate the expression of DMT1 and TFR1 thus increasing the uptake of NTBI and TBI by macrophages (Ludwiczek et al., 2003).”

In the citing paper

“In parallel, FPN1 levels are also reduced by transcriptional downregulation, which limits macrophage iron export and fosters iron storage in the cytoplasm (Ludwiczek et al., 2003;Yang et al., 2002).”

In the citing paper

“M2 cytokines like IL-10 - which are virtually absent in the proinflammatory M1 macrophages in nonhealing CVUs - are responsible for the release of iron from the macrophage to the extracellular space”

In the citing paper

“proinflammatory cytokines released at high concentrations from the unrestrained proinflammatory M1 macrophages further enhance the uptake and intracellular iron retention in macrophages by the induction of transmembrane transporter-1 expression”

In the citing paper

“Macrophage iron content is further expanded via an inhibitory effect of IFN-γ and LPS on ferroportin transcription thereby reducing cellular iron egress (Yang et al., 2002; Ludwiczek et al., 2003).”

In the citing paper

“DMT1 expression and iron transport capacity are increased in inflammatory MΦs (245); however, it has not been investigated whether this is also paralleled by increased accumulation of copper, zinc, or manganese in macrophages and whether or not this strengthens anti-microbial activities against M. tuberculosis.”

In the citing paper

“In the circulation there is also non-transferrin bound iron (NTBI) which can be taken up into the cell by ZIP- (ZRT/IRT-like protein)-14 or DMT1 (Ludwiczek et al., 2003; Liuzzi et al., 2006; Pinilla-Tenas et al., 2011; Figure 1);”

In the citing paper

“IFNγ has a strong regulatory role in iron homeostasis as it enhances the expression of cellular iron-regulating genes such as HO-1 but also reduces the iron-exporting gene ferroportin (Ludwiczek et al., 2003; Nairz et al., 2015).”

In the citing paper

“Tfr1, which is also known as CD71, is widely expressed by isolated macrophages, and it may form a major route of iron uptake in the absence of RBC (an indirect iron source), though it also appears to be important in adaptive immunity [103, 138].”

In the citing paper

“Specifically, macrophage functions driven by IFN-γ are impaired when macrophages are exposed to surplus iron [138, 162, 176] largely because iron directly inhibits the binding activities of the transcription factors nuclear factor interleukin-6 (NF-IL6) and hypoxia-inducible factor (HIF)-1α [55, 153] [176].”

In the citing paper

“Reduction in intracellular iron concentrations has been shown to promote the production of pro-inflammatory molecules such as TNF-α, IL-6, iNOS (nos2) or CCL-20 by activated macrophages (Weiss et al., 1994; Melillo et al., 1997; Ludwiczek et al., 2003; Oexle et al., 2003; Varesio et al., 2010), and these pathways are of importance for the control of intracellular pathogens like Salmonella (Andrews”

In the citing paper

“It is noteworthy that several cytokines impact on iron homeostasis mainly in macrophages by non-hepcidin mediated pathways thereby increasing iron uptake via different pathways but also by reducing erythrocyte half-life with subsequent stimulation of erythrophagocytosis, by promotion of iron storage within ferritin and by reduction cellular iron egress [172][173][174][175][176][177][178][179].”

In the citing paper

“Inflammation-driven Hamp induction thus causes iron sequestration within the mononuclear phagocyte system (MPS), which limits iron availability for extracellular pathogens (Bridle et al., 2003; Ludwiczek et al., 2003; Ganz, 2005; Theurl et al., 2008a).”

In the citing paper

“For instance, lipopolysaccharide as a component of the Gram-negative cell wall enhances HAMP production while stimulating DMT1 expression in myeloid cells, thereby favoring iron sequestration [35].”