Botulinum Toxin A Modulates Keratinocyte Proliferation and Inflammatory and Pruritic Mediators in Wound Healing

Botulinum toxin type A (BTA) is widely used in dermatologic procedures. While its anti-fibrotic effects on fibroblasts are well established, its role in keratinocyte-driven inflammation and pruritus during wound healing remains underexplored.

To evaluate the effects of BTA on keratinocyte proliferation, migration, and transforming growth factor-beta (TGF-β)-induced expression of inflammatory and pruritus-associated mediator.

Human epidermal keratinocytes were stimulated with TGF-β to mimic wound conditions, followed by BTA co-treatment. Cell proliferation and migration were assessed using water soluble tetrazolium salt-8 and scratch assays. Western blotting evaluated Smad2/3 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Reverse transcription-quantitative polymerase chain reaction was used to quantify inflammatory cytokines and itch-related mediators.

BTA significantly enhanced keratinocyte proliferation without affecting migration. It inhibited TGF-β-induced phosphorylation of Smad2/3 and ERK1/2. BTA also downregulated pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-α, monocyte chemotactic protein 1, prostaglandin E synthase) and pruritus-related mediators (IL-31, IL-33, cathepsin S, calcitonin gene-related peptide, substance P, and thymic stromal lymphopoietin).

BTA promotes keratinocyte proliferation and reduces TGF-β-induced inflammatory and pruritus-associated mediators. These findings suggest that BTA may facilitate wound healing by promoting keratinocyte proliferation while simultaneously modulating inflammation and pruritic responses.