Timed NF-B inhibition in skin reveals dual independent effects on development of HED/EDA and chronic inflammation

9Citations
Citations of this article
21Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

We have shown earlier that inhibiting NF-B activity in murine basal keratinocytes leads to hyperproliferation, inflammation, and cancer in a tumor necrosis factor receptor 1 (TNFR1)-dependent manner. We report here the outcomes of NF-B abrogation at different stages of epidermal morphogenesis using a conditional IBα transgenic mouse model. We find that blocking NF-B during embryogenesis mimics the epidermal and glandular defects seen in the human disease hypohidrotic/anhidrotic ectodermal dysplasia (HED/EDA), independently of the inflammatory phenotype and TNFR1. The onset of transgene expression after birth correlates with nuclear exclusion of the NF-B p50 subunit, hyperplasia, and development of a chronic inflammation initiated and dominated by macrophages. In this model, macrophages are important producers of the vascular endothelial growth factor A (VEGFA), whose inhibition attenuates the excessive angiogenesis otherwise observed. The inflammatory reaction requires the continuous suppression of NF-B in keratinocytes, indicating that an immune cell attractant(s) is directly induced in response to NF-B inhibition. As TNFα upregulation is a late event in this model, good candidates for such chemoattraction are the monocyte chemotactic proteins 1, 2, and 3 (MCP-1-2-3), which are upregulated in the epidermal compartment concomitantly with the onset of NF-B inhibition. © 2009 The Society for Investigative Dermatology.

Cite

CITATION STYLE

APA

Ulvmar, M. H., Sur, I., Mémet, S., & Toftgrd, R. (2009). Timed NF-B inhibition in skin reveals dual independent effects on development of HED/EDA and chronic inflammation. Journal of Investigative Dermatology, 129(11), 2584–2593. https://doi.org/10.1038/jid.2009.126

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free