Immunomodulatory Effects of Poly-D,L-Lactic Acid on LL-37-Driven Rosacea-like Inflammation via Suppression of mTORC1 Signaling.

In vitro and in vivo mechanistic study using cell lines and a mouse model

“To validate this hypothesis, we established an in vitro model using LL-37-treated human keratinocytes to determine whether PDLLA can reverse mTORC1-mediated inflammatory signaling. Subsequently, we analyzed an in vivo mouse model of rosacea-like inflammation induced by intradermal LL-37 injection.”

THP-1-derived macrophages, HaCaT keratinocytes, and female BALB/c mice

“Human monocytic THP-1 cells and immortalized human keratinocyte HaCaT cells were used for in vitro experiments.”

At least three independent biological replicates for experiments; specific mouse group sizes not explicitly stated in text

“All experiments were performed using at least three independent biological replicates.”

In vivo observation period up to 4 weeks post-injection; in vitro incubation periods of 24-48 hours

“Representative gross images were additionally collected at day 11 (immediately after material injection), day 25 (2 weeks after injection), and day 39 (4 weeks after injection).”

Conditioned media from PDLLA-treated macrophages suppressed mTORC1 activation and downstream inflammatory pathways in keratinocytes

“CMPDLLA attenuated downstream inflammatory responses, including NF-κB nuclear translocation, VEGF production, and NLRP3-inflammasome-mediated IL-18 secretion.”

PDLLA treatment reduced clinical lesion area and inflammatory infiltration in the mouse model

“Consequently, PDLLA treatment led to a pronounced reduction in clinical lesion area.”

Use of cell lines and a mouse model that may not fully recapitulate human rosacea; lack of positive drug comparator and IL-10 neutralization experiments

“First, the experimental models used here may not fully recapitulate the multifaceted nature of human rosacea.”