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J Dermatol Sci. 2019 Jan;93(1):58-64. doi: 10.1016/j.jdermsci.2018.12.004. Epub 2018 Dec 28.

Botulinum toxin blocks mast cells and prevents rosacea like inflammation.

Author information

1
Department of Dermatology, University of California, San Diego, CA, USA.
2
School of Medicine, University of California, San Diego, CA, USA.
3
Department of Anesthesiology and Pharmacology, University of California, San Diego, CA, USA.
4
Department of Dermatology, University of California, San Diego, CA, USA. Electronic address: adinardo@ucsd.edu.

Abstract

BACKGROUND:

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

OBJECTIVES:

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

METHODS:

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

RESULTS:

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

CONCLUSIONS:

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.

KEYWORDS:

Botox; Botulinum toxin; Mast cell; Mechanism of action; Rosacea

PMID:
30658871
DOI:
10.1016/j.jdermsci.2018.12.004
[Indexed for MEDLINE]

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