First Author | Du J | Year | 2014 |
Journal | J Pathol | Volume | 232 |
Issue | 3 | Pages | 356-68 |
PubMed ID | 24258200 | Mgi Jnum | J:207938 |
Mgi Id | MGI:5559962 | Doi | 10.1002/path.4302 |
Citation | Du J, et al. (2014) Epidermal overexpression of transgenic DeltaNp63 promotes type 2 immune and myeloid inflammatory responses and hyperplasia via NF-kappaB activation. J Pathol 232(3):356-68 |
abstractText | DeltaNp63 is known to be critical in skin development and cancer; however, how it triggers proliferation and inflammation in vivo remains to be elucidated. Here, we find that induced DeltaNp63 expression in skin of transgenic mice (TG) results in a hyperproliferative epidermis coupled with inflammatory infiltrates. In situ, infiltrating cells include CD45(+) leukocytes, CD19(+) B lymphocytes, CD3(+) T lymphocytes, CD4(+) T helper, CD25(+)/Foxp3(+) Treg, Ly6B(+) neutrophils, S-100(+) dendritic cells, and macrophages bearing CD11b(+), F4/80(+), CD68(+), and CD206(+) M2 type markers. Transcriptional profiling of TG skin revealed increased gene expression involved in inflammation and immune responses, including Th2/M2 cytokines and chemokines. These genes were co-regulated by DeltaNp63 and NF-kappaB RelA or cRel, and enhanced by TNF-alpha. Elevated cRel, RelA, and IKKs were observed in TG mouse skin and human squamous carcinomas with DeltaNp63 overexpression. Thus, our findings unveil a missing link connecting overexpressed DeltaNp63 with aberrant NF-kappaB activation, pro-inflammatory and type 2 cytokines and chemokines, and host infiltrates during skin inflammation and hyperplasia. Our findings provide a missing link between DeltaNp63 overexpression and NF-kappaB-mediated inflammation, of potential relevance to the pathogenesis of squamous carcinoma. |