| First Author | Kumari S | Year | 2014 |
| Journal | J Invest Dermatol | Volume | 134 |
| Issue | 10 | Pages | 2541-2550 |
| PubMed ID | 24739902 | Mgi Jnum | J:214775 |
| Mgi Id | MGI:5603988 | Doi | 10.1038/jid.2014.193 |
| Citation | Kumari S, et al. (2014) Epidermal RelA specifically restricts contact allergen-induced inflammation and apoptosis in skin. J Invest Dermatol 134(10):2541-50 |
| abstractText | Strong inhibition of NF-kappaB signaling in the epidermis results in spontaneous skin inflammation in mice and men. As there is evidence for linkage between polymorphisms within the NF-kappaB signaling pathway and human inflammatory skin phenotypes, we asked whether partial functional inhibition of NF-kappaB signaling in epidermal keratinocytes can modulate clinically relevant skin inflammation. We therefore mutated rela specifically in the epidermis of mice (RelA(E-MUT) mice). These mice show no inflammatory phenotype. Induction of contact allergy, but not croton oil-induced irritant dermatitis, resulted in stronger ear swelling and increased epidermal thickness in RelA(E-MUT) mice. Both contact allergen and croton oil treatment led to increased expression of calgranulins A and B (S100A8/A9) in RelA(E-MUT) mice. Epidermal hyperproliferation in RelA(E-MUT) mice was non-cell autonomous as cultured primary epidermal keratinocytes from RelA(E-MUT) mice showed reduced proliferation compared with controls. These results demonstrate that epidermal RelA specifically regulates delayed-type hypersensitivity-induced skin inflammation. In addition, we describe here an essential but nonspecific function of RelA in the protection of epidermal keratinocytes from apoptosis. Our study identifies functions of NF-kappaB signaling in the epidermis and corroborates a specific role of epidermal keratinocytes in the regulation of skin inflammation. |
