How the Cathelicidin Peptide LL-37 Drives Rosacea — and How Colchicine Blocks It | Research

The takeaway

Colchicine reduced rosacea symptoms in mice by blocking the interaction between the antimicrobial peptide LL-37 and TLR2 on neutrophils, reducing inflammation and redness.

LL-37 binds TLR2
Discovery that the cathelicidin peptide directly activates neutrophil inflammation through TLR2, explaining a key mechanism behind rosacea

What the researchers found

LL-37 cathelicidin directly binds to TLR2 on neutrophils to drive rosacea inflammation, and colchicine disrupts this binding, reducing inflammatory markers, NET formation, and rosacea-like symptoms in mice.

Why it matters

This study reveals the specific molecular mechanism by which the peptide LL-37 causes rosacea — by binding TLR2 on neutrophils. Understanding this peptide-receptor interaction could lead to more targeted treatments for the millions of people living with rosacea.

The numbers in context

Colchicine reduced redness scores, inflammatory biomarkers, and neutrophil infiltration in the rosacea mouse model.

How the study worked

LL-37-induced rosacea mouse model treated with colchicine. Assessed skin redness scores, inflammatory biomarkers via RT-PCR, neutrophil infiltration via immunohistochemistry, NET formation, and TLR2-LL-37 binding via coimmunoprecipitation. Validated with bioinformatics analysis.

Who was studied

Mice with LL-37 cathelicidin-induced rosacea model

What this study cannot tell us

Mouse rosacea model induced by external LL-37 injection may not fully replicate human disease, where LL-37 overproduction is endogenous. Colchicine has gastrointestinal and other side effects that need clinical evaluation in rosacea patients. No human trial data.

How to read the evidence

Preliminary evidence: well-designed mouse model study with clear mechanistic findings, but no human clinical data yet.

When this study was published

Published in 2024. Provides new mechanistic insights into cathelicidin-driven rosacea.

The bigger picture

LL-37 is a key antimicrobial peptide in human skin defense, but its overexpression is a known driver of rosacea. This study maps out the specific inflammatory pathway — LL-37 → TLR2 → neutrophil activation → NETs — providing a roadmap for targeted interventions. Colchicine, already approved for gout and other inflammatory conditions, could potentially be repurposed for rosacea.

Questions still open

Would colchicine be effective and tolerable in human rosacea patients, given its known side effect profile?
Could drugs that specifically block the LL-37-TLR2 interaction be developed as targeted rosacea treatments?
Does this TLR2 pathway also explain the flare patterns seen in different rosacea subtypes?

Common questions

What role does the peptide LL-37 play in rosacea?

LL-37 (cathelicidin) is an antimicrobial peptide that normally helps protect skin from infections. In rosacea, it is overproduced and triggers excessive inflammation by binding to TLR2 receptors on neutrophils, causing redness, swelling, and pustules.

Could colchicine become a rosacea treatment?

This mouse study suggests it could work by blocking the LL-37-TLR2 inflammatory pathway. Colchicine is already prescribed for gout and other inflammatory conditions, which could speed up its evaluation for rosacea. However, human trials are needed first.

Read the original research

Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway.

Inflammation, 47(3), 1002-1014

View on PubMed ↗Publisher’s paper ↗

Citation

Yuan, Xin; Sheng, Liang; Shi, Guang; Jiang, Leiwei; Lian, Chengxiang. (2024). Colchicine Alleviates Rosacea by Inhibiting Neutrophil Inflammation Activated by the TLR2 Pathway.. Inflammation, 47(3), 1002-1014. https://doi.org/10.1007/s10753-023-01956-6