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Epidermal overexpression of transgenic ΔNp63 promotes type 2 immune and myeloid inflammatory responses and hyperplasia via NF-κB activation. - PubMed - NCBI
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J Pathol. 2014 Feb;232(3):356-68. doi: 10.1002/path.4302.

Epidermal overexpression of transgenic ΔNp63 promotes type 2 immune and myeloid inflammatory responses and hyperplasia via NF-κB activation.

Author information

1
Clinical Genomics Unit and Tumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD, 20892, USA; Central Laboratory, Nanshan Hospital, Guangdong Medical College, Shenzhen, Guangdong, 518052, China.

Abstract

ΔNp63 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 ΔNp63 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 ΔNp63 and NF-κB RelA or cRel, and enhanced by TNF-α. Elevated cRel, RelA, and IKKs were observed in TG mouse skin and human squamous carcinomas with ΔNp63 overexpression. Thus, our findings unveil a missing link connecting overexpressed ΔNp63 with aberrant NF-κB activation, pro-inflammatory and type 2 cytokines and chemokines, and host infiltrates during skin inflammation and hyperplasia. Our findings provide a missing link between ΔNp63 overexpression and NF-κB-mediated inflammation, of potential relevance to the pathogenesis of squamous carcinoma.

KEYWORDS:

NF-κB; chemokines; cytokines; infiltrating cells; transgenic mouse; Δp63

PMID:
24258200
DOI:
10.1002/path.4302
[Indexed for MEDLINE]
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