PubMed RSS Feed - -Aging-conferred SIRT7 Decline Inhibits Rosacea-like Skin Inflammation via Modulating TLR2-NF-κB Signaling

[rss]

J Invest Dermatol. 2022 Apr 9:S0022-202X(22)00273-1. doi: 10.1016/j.jid.2022.03.026. Online ahead of print.

ABSTRACT

Rosacea is a chronic inflammatory skin disorder that manifests abnormal enhanced sensitivity to environment stimuli. The decreased prevalence of rosacea in aged population has been reported, but the underlying mechanism is unclear. Here we confirm that the rosacea-like skin inflammation induced by Cathelicidin LL37 is alleviated in aged mice and mice with progeria. Primary mouse keratinocytes isolated from aged mice and human dermal fibroblasts (HDFs) that undergo senescence present a much lower sensitivity to pro-inflammatory stimuli. Mechanistically, toll-like receptor 2 (TLR2) is downregulated in the skin of both aged population and mice. Knockdown of TLR2 in young HDFs mimics the attenuated immune response to LL37 and TNFα evidenced in aged HDFs, while overexpression of TLR2 in aged HDFs rescued this attenuation. At the molecular level, in response to inflammatory stimuli SIRT7 mediates the upregulation of TLR2, which promotes the activation of NF-κB signaling. The decay of SIRT7 confers age-related decline of TLR2-NF-κB signaling. While overexpression of exogenous Sirt7 abrogates skin immune reactivity reduction in aged mice, loss of Sirt7 alleviates the rosacea-like features in mice. Thus, we reveal a SIRT7-TLR2-NF-κB axis that can be targeted for the improvement of rosacea.

PMID:35413292 | DOI:10.1016/j.jid.2022.03.026

{url} = URL to article