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| <<snip>>
Our results suggest modulation of iron metabolism as a potential approach for
anti-inflammatory therapy.
<<snip>>
Cell. 2004 Nov 12;119(4):529-42. Related Articles, Links
Ferritin Heavy Chain Upregulation by NF-kappaB Inhibits TNFalpha-Induced
Apoptosis by Suppressing Reactive Oxygen Species.
Pham CG, Bubici C, Zazzeroni F, Papa S, Jones J, Alvarez K, Jayawardena S, De
Smaele E, Cong R, Beaumont C, Torti FM, Torti SV, Franzoso G.
The Ben May Institute for Cancer Research and The university of Chicago, 924
East 57th Street, Chicago, IL 60637 USA.
During inflammation, NF-kappaB transcription factors antagonize apoptosis
induced by tumor necrosis factor (TNF)alpha. This antiapoptotic activity of
NF-kappaB involves suppressing the accumulation of reactive oxygen species
(ROS) and controlling the activation of the c-Jun N-terminal kinase (JNK)
cascade. However, the mechanism(s) by which NF-kappaB inhibits ROS accumulation
is unclear. We identify ferritin heavy chain (FHC)-the primary iron storage
factor-as an essential mediator of the antioxidant and protective activities of
NF-kappaB. FHC is induced downstream of NF-kappaB and is required to prevent
sustained JNK activation and, thereby, apoptosis triggered by TNFalpha.
FHC-mediated inhibition of JNK signaling depends on suppressing ROS
accumulation and is achieved through iron sequestration. These findings
establish a basis for the NF-kappaB-mediated control of ROS induction and
identify a mechanism by which NF-kappaB suppresses proapoptotic JNK signaling.
Our results suggest modulation of FHC or, more broadly, of iron metabolism as a
potential approach for anti-inflammatory therapy.
PMID: 15537542 [PubMed - in process]
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Tom
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