Superoxide Dismutase 3 Inhibits LL-37/KLK-5-Mediated Skin Inflammation through Modulation of EGFR and Associated Inflammatory Cascades.
Agrahari. Gaurav G; Sah. Shyam Kishor SK; Nguyen. Cuong Thach CT; Choi. Sung Sik SS; Kim. Hae-Young HY; Kim. Tae-Yoon TY
Key Findings
- SOD3 sharply lowered the production of inflammatory molecules triggered by LL‑37 or KLK‑5 in human skin cells.
- SOD3 blocked activation of several inflammation pathways, including EGFR, PAR‑2, NLRP3, and MAPK (p38/ERK).
- In mice lacking SOD3, skin inflammation after KLK‑5 injection was worse, but giving SOD3 back rescued the skin and reduced inflammation.
Practical Outcomes
- For DIY health enthusiasts, the study suggests that boosting SOD3 activity could be a strategy to protect skin from inflammation linked to LL‑37/KLK‑5, which are involved in conditions like acne, rosacea, and psoriasis. However, SOD3 is not currently available as an over‑the‑counter supplement, so practical application would likely require experimental topical formulations or gene‑based approaches, limiting immediate use.
Summary
Scientists found that an enzyme called superoxide dismutase 3 (SOD3) can calm down skin inflammation caused by the antimicrobial peptide LL‑37 and the enzyme KLK‑5. In lab cells and mice, adding SOD3 reduced redness, swelling, and the chemical signals that drive skin irritation.
Abstract
The expressions of LL-37 and KLK-5 were found to be altered in various dermatoses, including atopic dermatitis, psoriasis, and rosacea. However, the downstream inflammatory effect of LL-37 and KLK-5 is not as well studied. In addition, there is little high-quality evidence for the treatment of LL-37- and KLK-5-mediated inflammation. In this study, we investigated the effect of superoxide dismutase 3 (SOD3) on LL-37- or KLK-5-induced skin inflammation in vitro and in vivo and its underlying anti-inflammatory mechanisms. Our data showed that SOD3 significantly reduced both LL-37- and KLK-5-induced expression of pro-inflammatory mediators and suppressed the activation of EGFR, protease-activated receptor 2, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, and p38/extracellular signal-regulated kinase signaling pathways in human keratinocytes. Moreover, SOD3 suppressed LL-37-induced expression of inflammatory mediators, reactive oxygen species production, and p38/extracellular signal-regulated kinase activation in mast cells. In addition, subcutaneous injection of KLK-5 in SOD3 knockout mice exhibited erythema with increased epidermal thickness, mast cell and neutrophil infiltration, expression of inflammatory mediators, and activation of EGFR, protease-activated receptor 2, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3, and downstream mitogen-activated protein kinase pathways. However, treatment with SOD3 in SOD3 knockout mice rescued KLK-5-induced inflammatory cascades. Similarly, KLK-5-induced inflammation in wild-type mice was also ameliorated when treated with SOD3. Taken together, our data suggest that SOD3 is a potentially effective therapy for both LL-37-and KLK-5-induced skin inflammation.
Study Information
pubmed
2019
2019-08-26T00:00:00.000Z
10.1016/j.jid.2019.08.434
26
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