A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis.
Takahashi. T T; Asano. Y Y; Nakamura. K K; Yamashita. T T; Saigusa. R R; Ichimura. Y Y; Toyama. T T; Taniguchi. T T; Yoshizaki. A A; Tamaki. Z Z; Tada. Y Y; Sugaya. M M; Kadono. T T; Sato. S S
Key Findings
- LL-37 levels are increased in skin cells, small vessels, and serum of systemic sclerosis patients
- Higher LL-37 levels correlate with worse skin scores, lung involvement, and presence of digital ulcers
- Deficiency of the transcription factor Fli1 leads to more LL-37 production in endothelial cells, suggesting a mechanistic link to fibrosis and vasculopathy
Practical Outcomes
- For biohackers, the data imply that raising LL‑37 (through supplements or lifestyle changes) could potentially worsen fibrotic or vascular issues, so it’s best to avoid strategies aimed at increasing this peptide unless you have a clear medical reason. There are no actionable dosing protocols or performance benefits shown, making the findings of limited direct use for longevity or performance optimization.
Summary
The research shows that the antimicrobial peptide LL‑37 is higher in the skin and blood of people with systemic sclerosis and appears to worsen skin thickening, lung disease, and digital ulcers, linking it to fibrosis and blood‑vessel damage.
Abstract
LL-37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc). To elucidate the potential role of LL-37 in SSc. The expression of target molecules was evaluated by immunostaining and quantitative reverse-transcription real-time polymerase chain reaction in human and murine skin. The mechanisms regulating LL-37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL-37 levels were determined by enzyme-linked immunosorbent assay. In SSc lesional skin, LL-37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon-α expression, possibly reflecting LL-37-dependent induction of interferon-α. In SSc animal models, bleomycin-treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL-37, similar to that of LL-37 in SSc lesional skin. Furthermore, Fli1<sup>+/-</sup> mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL-37 gene) promoter and Fli1 deficiency-dependent induction of LL-37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL-37 levels significantly higher than in healthy controls. Furthermore, serum LL-37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without. LL-37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.
Study Information
pubmed
2016
2016-08-30T00:00:00.000Z
10.1111/bjd.14699
40
42