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Topical hypochlorite ameliorates NF-?B-mediated skin diseases in mice.

ABSTRACT: Nuclear factor-?B (NF-?B) regulates cellular responses to inflammation and aging, and alterations in NF-?B signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-?B-dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-?B kinase (IKK), a key regulator of NF-?B activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-?B reporter mice, topical HOCl reduced LPS-induced NF-?B signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-?B-driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-?B-dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-?B-mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims.

SUBMITTER: Leung TH

PROVIDER: S-EPMC3859383 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice.

Leung Thomas H TH Zhang Lillian F LF Wang Jing J Ning Shoucheng S Knox Susan J SJ Kim Seung K SK

The Journal of clinical investigation 20131115 12

Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB-dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB ...[more]

PMID: 24231355

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Topical hypochlorite ameliorates NF-?B-mediated skin diseases in mice.

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Topical hypochlorite ameliorates NF-κB-mediated skin diseases in mice.

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