Human antimicrobial peptide LL-37 modulates proinflammatory responses induced by cytokine milieus and double-stranded RNA in human keratinocytes.
Chen. Xue X; Takai. Toshiro T; Xie. Yang Y; Niyonsaba. François F; Okumura. Ko K; Ogawa. Hideoki H
Key Findings
- LL-37 (25 µg/mL) suppresses dsRNA‑induced TSLP, CCL5, CXCL10, and later CXCL8 production in human keratinocytes.
- LL-37 enhances early CXCL8 release and boosts CXCL8 and IL‑6 when paired with IL‑17/IL‑22 (Th17 cytokines).
- A reversed‑sequence LL-37 peptide mimics the effects of native LL-37, whereas a scrambled peptide shows no activity.
Practical Outcomes
- For DIY skin‑health experiments, LL-37 might be useful to modulate specific inflammatory pathways, but the effective concentration is quite high and not easily achievable with typical topical formulations. The peptide could theoretically help reduce TSLP‑driven atopic dermatitis while possibly worsening IL‑17/IL‑22‑driven psoriasis. Until safe, practical delivery methods are developed, LL-37 remains more of a research tool than a ready‑to‑use biohacker supplement.
Summary
The study shows that the human peptide LL-37 can both calm and boost certain skin inflammation signals depending on the situation. At a relatively high dose, it blocks some inflammatory molecules triggered by viral‑like RNA, but it also ramps up others, especially when combined with skin‑related cytokines like IL‑17 and IL‑22. A reversed‑sequence version works similarly, while a scrambled version does not.
Abstract
Epidermal keratinocytes produce proinflammatory cytokines/chemokines upon stimulation with cytokine milieus and Toll-like receptor ligands, which are considered to reflect epidermal environments in inflamed skin. The human antimicrobial peptide LL-37, besides having microbicidal functions, plays multiple roles as a "host defense peptide" in the immune system. Here, we examined the effect of LL-37 on proinflammatory responses induced by double-stranded RNA (dsRNA) and cytokines in primary human keratinocytes. LL-37 inhibited dsRNA-induced production of thymic stromal lymphopoietin (TSLP), CCL5/RANTES, CXCL10/IP-10, and CXCL8/IL-8, which was attributable to interaction between LL-37 and dsRNA, although LL-37 upregulated CXCL8 expression at an earlier time point (8 h). LL-37 inhibited the increase of CXCL10 and CCL5 induced by TNF-α- and/or IFN-γ but enhanced that of CXCL8. LL-37 and Th17 cytokines (IL-17 and IL-22) synergistically upregulated the expression of CXCL8 and IL-6. LL-37 showed the effects above at a high concentration (25 μg/ml, 5.6 μM). We also examined effects of a peptide with a scrambled LL-37 sequence, which has been frequently used as a negative control, and those of another peptide with the reversed LL-37 sequence, activities of which have not been well investigated. Interestingly, the reversed LL-37 had effects similar to LL-37 but the scrambled LL-37 did not. The modulation by LL-37 of the keratinocyte proinflammatory responses induced by cytokine milieus and dsRNA suggests novel roles for LL-37 in skin inflammation such as the promotion of IL17/IL-22/IL-6-associated psoriasis and suppression of TSLP-associated atopic dermatitis.
Study Information
pubmed
2013
2013-03-20T00:00:00.000Z
10.1016/j.bbrc.2013.03.024
86
37