The human cathelicidin LL-37 host defense peptide upregulates tight junction-related proteins and increases human epidermal keratinocyte barrier function.
Akiyama. Toshihiro T; Niyonsaba. François F; Kiatsurayanon. Chanisa C; Nguyen. Toan The TT; Ushio. Hiroko H; Fujimura. Tsutomu T; Ueno. Takashi T; Okumura. Ko K; Ogawa. Hideoki H; Ikeda. Shigaku S
Key Findings
- LL‑37 increases the levels and membrane placement of tight‑junction proteins like claudins and occludin in human keratinocytes.
- Treating keratinocyte layers with LL‑37 raises electrical resistance and lowers paracellular permeability, indicating a stronger barrier.
- The barrier‑enhancing effect depends on Rac1, atypical PKC, GSK‑3, and PI3K signaling; blocking these pathways or using a claudin inhibitor stops the benefit.
Practical Outcomes
- For DIY skin‑health protocols, LL‑37 appears to be a promising candidate to reinforce the skin’s barrier, which could help with dryness, irritation, or barrier‑related conditions. However, the work is limited to cell‑culture experiments, so optimal dosing, formulation, safety, and real‑world efficacy remain unknown. Until human studies are available, any use would be experimental and should be approached with caution.
Summary
The study shows that the natural peptide LL‑37 can boost proteins that seal skin cells together, making the skin barrier tighter and less leaky. It does this by turning on several cell‑signaling pathways, and the effect disappears if those pathways are blocked.
Abstract
Both psoriasis and atopic dermatitis (AD) are not only associated with an impaired stratum corneum barrier, but also with abnormal expression of the tight junction (TJ) proteins. Because host defense peptides, including LL-37, are overexpressed in lesional psoriatic skin but are downregulated in lesional AD skin, we hypothesized that LL-37 might regulate the TJ function in keratinocytes. We demonstrated that LL-37 selectively increased the expression of several claudins and occludin, and enhanced their membrane distribution. Furthermore, LL-37 elevated the transepithelial electrical resistance while reducing the paracellular permeability of keratinocyte layers, and this activity was weakened by the claudin inhibitor ochratoxin A. A characterization of the molecular mechanism underlying the regulation of the TJ barrier by LL-37 revealed that LL-37 induced the activation of the Rac1, atypical PKC, glycogen synthase kinase-3 and PI3K pathways, and the specific inhibition of these pathways reversed the LL-37-mediated regulation of TJ function. In addition, LL-37 enhanced the expression of differentiation markers under the control of ochratoxin A, suggesting an association between LL-37-induced TJ function and keratinocyte differentiation. These data provide novel evidence that, in addition to its antimicrobial and other immunoregulatory functions, LL-37 contributes to cutaneous immunity by strengthening the skin's barrier function.
Study Information
pubmed
2014
2014-05-23T00:00:00.000Z
10.1159/000362789
100
46