| First Author | Liu B | Year | 2011 |
| Journal | Cell Death Differ | Volume | 18 |
| Issue | 12 | Pages | 1854-64 |
| PubMed ID | 21566664 | Mgi Jnum | J:201800 |
| Mgi Id | MGI:5515805 | Doi | 10.1038/cdd.2011.56 |
| Citation | Liu B, et al. (2011) IKKalpha represses a network of inflammation and proliferation pathways and elevates c-Myc antagonists and differentiation in a dose-dependent manner in the skin. Cell Death Differ 18(12):1854-64 |
| abstractText | Inhibitor of nuclear factor kappaB kinase-alpha (IKKalpha) is required for maintaining skin homeostasis and preventing skin tumorigenesis. However, its signaling has not been extensively investigated. In the present study, we generated two mouse lines that expressed different levels of transgenic IKKalpha in the basal epidermis under the control of keratin-5 promoter and further evaluated their effects on the major pathways of inflammation, proliferation, and differentiation in the skin. Regardless of the transgenic IKKalpha levels, the mice develop normally. Because IKKalpha deletion in keratinocytes blocks terminal differentiation and induces epidermal hyperplasia and skin inflammation, we depleted the endogenous IKKalpha in these transgenic mice and found that the transgenic IKKalpha represses epidermal thickness and induces terminal differentiation in a dose-dependent manner. Also, transgenic IKKalpha was found to elevate expression of Max dimer protein 1 (Mad1) and ovo-like 1, c-Myc antagonists, but repress activities of epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), Jun-amino-terminal kinases, c-Jun, signal transducer and activator of transcription 3 (Stat3), and growth factor levels in a dose-dependent fashion in the skin. Moreover, EGFR reduction represses IKKalpha deletion-induced excessive ERK, Stat3 and c-Jun activities, and skin inflammation. These new findings indicate that elevated IKKalpha expression not only represses epidermal thickness and induces terminal differentiation, but also suppresses skin inflammation by an integrated loop. Thus, IKKalpha maintains skin homeostasis through a broad range of signaling pathways. |
