Cathelicidin LL-37 Ignites Primed NLRP3 Inflammasomes in Rosacea.
Croitoru. David O DO; Piguet. Vincent V
Key Findings
- LL‑37 levels increase after microbial infection, UV exposure, or skin injury
- LL‑37 promotes NLRP3 inflammasome activation via lysosomal damage when LPS is present
- Injecting LL‑37 into mouse skin causes inflammation that is prevented by NLRP3 inhibition or knockout
Practical Outcomes
- For DIY health enthusiasts, the takeaway is to minimize factors that boost LL‑37—like excessive UV exposure or skin barrier damage—to avoid triggering rosacea‑like inflammation. There’s no suggested benefit of adding LL‑37, and caution is advised if using products that might raise its levels.
Summary
The study shows that the skin peptide LL‑37, which rises after UV light, infections or injury, can trigger a strong inflammatory response in rosacea by activating a cellular alarm called the NLRP3 inflammasome. In mouse skin, injecting LL‑37 caused redness and swelling, but blocking NLRP3 stopped the reaction.
Abstract
Microbes and commensal mites contribute to the development of inflammation and neurovascular dysregulation in rosacea. Cathelicidin family proteins are epithelial antimicrobial peptides expressed in higher-order mammals. In humans, mature LL-37 is cleaved from its precursor in response to microbial infection, UV light, and injury. In their new article in the Journal of Investigative Dermatology, Yoon et al. expand on existing evidence supporting LL-37 proinflammatory activity in lipopolysaccharide (LPS)- and UV-primed models of rosacea. They show in vitro that LL-37 promotes NLRP3-mediated inflammasome activation through lysosomal destabilization in the presence of LPS and that the injection of LL-37 in vivo leads to skin inflammation that is abrogated by direct NLRP3 inhibition and homozygous knockout in a murine model.
Study Information
pubmed
2021
2021-09-23T00:00:00.000Z
10.1016/j.jid.2021.04.024
10
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