NF-kappa B activation / iron



Comp Hepatol. 2004 Jan 14;3 Suppl 1:S36. Links

Signaling role of iron in NF-kappa B activation in hepatic macrophages.

Xiong S, She H, Tsukamoto H.

Department of Pathology, Keck School of Medicine, University of Southern California, USA.
[email protected]

Iron is both essential and toxic for cells and impaired iron homeostasis has been shown to cause or
potentiate various forms of liver injury. Research in our laboratory suggests that iron also plays a
pivotal role in intracellular signaling for NF-kappa B activation in hepatic macrophages (HM). Our
results showed: 1) HM from alcohol-fed rats had a increase in the nonheme iron content accompanied
by NF-kappa B activation; 2) iron chelation normalized nonheme iron concentration and blocked
enhanced NF-kappa B activation and TNF-alpha expression in these cells; 3) LPS-induced NF-kappa B
activation was also blocked by iron chelator; 4) iron directly induced TNF-alpha expression via IKK
and NF-kappa B activation in normal HM. We propose that iron acts as an independent proinflammatory
molecule via induction of the intracellular signaling for NF-kappa B activation in HM and primes the
liver for chronic inflammation and injury.

PMID: 14960188 [PubMed - as supplied by publisher]


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