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Activation of IKK2‐NF‐κB in adult mouse liver produces a cytoprotective gene expression profile without signs of inflammation, insulin resistance, or fibrosis (1115.4)
Author(s) -
Lu Hong,
Lei Xiaohong,
Zhang Qinghao
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1115.4
Subject(s) - relb , insulin resistance , inflammation , proinflammatory cytokine , fibrosis , nfkb1 , endocrinology , biology , cancer research , medicine , insulin , biochemistry , gene , transcription factor
The NF‐kB signaling, regulated by IKK1 and IKK2, is activated by various stresses to protect or damage the liver, in context‐specific manners. Two studies of liver‐specific expression of constitutive active IKK2 (Ikk2ca) showed that activation of IKK2‐NF‐kB in developing liver caused inflammation, insulin resistance, and/or fib r osis. The purpose of this study was to understand how activation of IKK2‐NF‐kB in adult liver alters gene expression and pathophysiology. Using Ikk2ca knockin and Alb‐cre mice, we generated mice with adult hepatocyte‐specific activation of IKK2 (Liv‐Ikk2ca). Adult male Liv‐Ikk2ca mouse livers had induction of mRNAs of Ikk2 and classical NF‐kB targets, as well as IKK1, NIK (activator of IKK1), and RelB, but no changes in markers of inflammation or fibrosis (by real‐time PCR). Liv‐Ikk2ca mice had reduction of prooxidative Cyp2e1 and Cyp4a14, induction of antioxidative Nqo1 and Sod2, but no changes of key enzymes in fatty acid oxidation and gluconeogenesis. Regarding nuclear proteins of NF‐kB subunits, Liv‐Ikk2ca mice had moderate increase in p50, strong increase in RelB, but no changes in p65 (by Western blot). In summary, IKK2‐NF‐kB activation in normal adult hepatocytes produces a cytoprotective gene expression profile without signs of inflammation, insulin resistance, or fibrosis, likely due to strong activation of the IKK1‐regulated antiinflammatory alternative NF‐kB pathway.