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Updated: May 20, 2026
Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
Involvement of serine protease and proteinase-activated receptor 2 in dermatophyte-associated itch in mice
Tsugunobu Andoh1, Yusuke Takayama, Takako Yamakoshi
1Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Abstract:
We investigated the involvement of serine protease and proteinase-activated receptor 2 (PAR(2)) in dermatophyte-induced itch in mice. An intradermal injection of an extract of the dermatophyte Arthroderma vanbreuseghemii (ADV) induced hind-paw scratching, an itch-related behavior. ADV extract-induced scratching was inhibited by the opioid receptor antagonists naloxone and naltrexone, the serine protease inhibitor nafamostat mesylate, and the PAR(2) receptor antagonist FSLLRY-NH(2). ADV extract-induced scratching was not inhibited by the H(1) histamine receptor antagonist terfenadine or by mast cell deficiency. Heat pretreatment of the ADV extract markedly reduced the scratch-inducing and serine protease activities. Proteolytic cleavage within the extracellular N terminus of the PAR(2) receptor exposes a sequence that serves as a tethered ligand for the receptor. The ADV extract as well as tryptase and trypsin cleaved a synthetic N-terminal peptide of the PAR(2) receptor. The present results suggest that serine protease secreted by dermatophytes causes itching through activation of the PAR(2) receptors, which may be a causal mechanism of dernatophytosis itch.
Insights
Dermatophyte fungi trigger itch by releasing serine proteases that activate proteinase-activated receptor 2 (PAR2). This research uncovers a key mechanism behind fungal-induced itching.
Area of Science:
- Dermatology
- Immunology
- Biochemistry
Background:
- Itch is a common symptom of fungal skin infections.
- The specific mechanisms driving dermatophyte-induced itch are not fully understood.
Purpose of the Study:
- To investigate the role of serine proteases and proteinase-activated receptor 2 (PAR2) in mediating itch caused by the dermatophyte Arthroderma vanbreuseghemii (ADV) in a mouse model.
Main Methods:
- Intradermal injection of ADV extract into mouse hind paws to induce scratching behavior.
- Administration of various receptor antagonists (opioid, PAR2, H1 histamine) and a serine protease inhibitor.
- Assessment of the effects of heat treatment on ADV extract activity.
- In vitro cleavage assays using synthetic peptides of the PAR2 receptor.
Main Results:
- ADV extract induced significant scratching behavior, which was reduced by opioid antagonists, a serine protease inhibitor, and a PAR2 antagonist.
- Histamine receptor antagonism and mast cell deficiency did not inhibit scratching.
- Heat treatment abolished the scratch-inducing and serine protease activities of the ADV extract.
- ADV extract, tryptase, and trypsin demonstrated proteolytic activity on a synthetic PAR2 N-terminal peptide.
Conclusions:
- Serine proteases secreted by dermatophytes activate PAR2 receptors, leading to itch sensation.
- This pathway represents a potential mechanism for itch associated with dermatophytosis.
- Targeting serine proteases or PAR2 may offer therapeutic strategies for fungal-induced itch.
