Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria

FASEB J. 2024 May 15;38(9):e23641. doi: 10.1096/fj.202400146R.

Abstract

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Keywords: acetylcholinesterase; cholinergic urticaria; inflammation; keratinocyte; ultraviolet B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholinesterase* / genetics
  • Acetylcholinesterase* / metabolism
  • Animals
  • Humans
  • Keratinocytes* / metabolism
  • Keratinocytes* / radiation effects
  • Male
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Skin* / metabolism
  • Skin* / radiation effects
  • Ultraviolet Rays* / adverse effects
  • Urticaria* / etiology
  • Urticaria* / metabolism

Substances

  • Acetylcholinesterase
  • MicroRNAs
  • Acetylcholine