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Differential activation of nuclear factor‐kappa B in healing tissue of poor healer SJL strain and good healer MRL strain: Implications in wound repair and regeneration
Author(s) -
Kumar Ashok,
Dogra Charu,
Baylink David J.,
Mohan Subburaman
Publication year - 2006
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.20.5.lb121-b
Subject(s) - inflammation , transcription factor , wound healing , proinflammatory cytokine , p50 , nfkb1 , nf κb , microbiology and biotechnology , iκbα , kinase , electrophoretic mobility shift assay , immunology , biology , cancer research , gene , genetics
Adult wound repair is characterized by three main overlapping and interconnected phases, namely periods of inflammation, proliferation, and scar formation. Although mild inflammatory response is required for wound repair, excessive inflammation generally leads to incomplete healing and scar formations. To examine if differences in inflammation contribute to why MRL but not SJL mice regenerates faster ear punch hole we measured the expression level of transcription factors known to be involved in inflammation of healing tissue using transcription factor array. Although the activity of several transcription factors was increased in the healing tissue of both MRL and SJL mice, the level of activation of nuclear factor‐kappa B (NF‐κB), a proinflammatory transcription factor, was substantially higher in healing tissue of SJL mice than MRL mice. Electrophoretic mobility shift assay confirmed the increased DNA‐binding activity of NF‐κB in SJL than MRL mice. Super‐shift analysis of NF‐κB/DNA complex revealed that activated NF‐κB consisted p50, c‐Rel and Bcl‐3 proteins. The increased activation of NF‐κB in SJL mice was associated with a concomitant increase in IκB kinase activity and the phosphorylation and degradation of IκBα protein. NF‐κB pathway‐specific oligo GEarray showed increased expression of several genes that are either involved in the activation of NF‐κB or are direct transcriptional target of NF‐κB. Collectively our data suggest that higher activation of NF‐κB might contribute to the poor would healing in SJL mice compared to MRL mice.