Minocycline inhibits rosacea-like inflammation through the TLR4-mediated NF-κB signaling pathway in vivo and in vitro

PLoS One. 2025 May 16;20(5):e0323598. doi: 10.1371/journal.pone.0323598. eCollection 2025.

Abstract

Background: Rosacea is a chronic inflammatory skin disease characterized by multiple intricate pathogenic factors. Previous studies have substantiated the anti-inflammatory properties of minocycline and its potential therapeutic efficacy in treating rosacea. However, further elucidation of the underlying mechanism is warranted.

Methods: HaCaT cells and BALB/c mice were treated with LL37. Moreover, the effect of minocycline on rosacea was explored through the addition of an NF-κB inhibitor (PDTC) or overexpression of Toll-like receptor 4 (TLR4). The expression of related markers was detected by western blotting, immunofluorescence, ELISA, flow cytometry, etc.

Results: Minocycline suppressed dermal infiltration of inflammatory cells in rosacea-like mice and reduced the expression of inflammatory cytokines in rosacea-like mice and cells. Moreover, minocycline downregulated the expression of TLR4 and p-NF-κB thereby inhibiting ROS production. However, overexpression of TLR4 or the addition of PDTC counteracted the effects of minocycline by promoting cellular inflammation and ROS production. Mechanistically, minocycline hinders TLR4/TNF-α activation induced by LL37 in skin and cells to suppress the expression of inflammatory cytokines.

Conclusion: Minocycline alleviates inflammation progression in rosacea by downregulating TLR4 and inhibiting the activation of the NF-κB pathway, providing a scientific basis for subsequent clinical treatment.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Cathelicidins
  • Cytokines / metabolism
  • HaCaT Cells
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / metabolism
  • Inflammation* / pathology
  • Mice
  • Mice, Inbred BALB C
  • Minocycline* / pharmacology
  • Minocycline* / therapeutic use
  • NF-kappa B* / metabolism
  • Reactive Oxygen Species / metabolism
  • Rosacea* / drug therapy
  • Rosacea* / metabolism
  • Rosacea* / pathology
  • Signal Transduction* / drug effects
  • Toll-Like Receptor 4* / genetics
  • Toll-Like Receptor 4* / metabolism

Substances

  • Toll-Like Receptor 4
  • Minocycline
  • NF-kappa B
  • Reactive Oxygen Species
  • Cathelicidins
  • TLR4 protein, human
  • Cytokines
  • Anti-Inflammatory Agents