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Research ArticleInflammation, Immunopharmacology, and Asthma

Involvement of Serine Protease and Proteinase-Activated Receptor 2 in Dermatophyte-Associated Itch in Mice

Tsugunobu Andoh, Yusuke Takayama, Takako Yamakoshi, Jung-Bum Lee, Ayako Sano, Tadamichi Shimizu and Yasushi Kuraishi
Journal of Pharmacology and Experimental Therapeutics October 2012, 343 (1) 91-96; DOI: https://doi.org/10.1124/jpet.112.195222
Tsugunobu Andoh
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Yusuke Takayama
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Takako Yamakoshi
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Jung-Bum Lee
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Ayako Sano
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Tadamichi Shimizu
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Yasushi Kuraishi
Departments of Applied Pharmacology (T.A., Y.T., Y.K.), Dermatology (T.Y., T.S.), and Pharmacognosy (J.-B.L.), Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan; and Graduate School of Agriculture, University of the Ryukyu, Okinawa, Japan (A.S.)
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Abstract

We investigated the involvement of serine protease and proteinase-activated receptor 2 (PAR2) 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 PAR2 receptor antagonist FSLLRY-NH2. ADV extract-induced scratching was not inhibited by the H1 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 PAR2 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 PAR2 receptor. The present results suggest that serine protease secreted by dermatophytes causes itching through activation of the PAR2 receptors, which may be a causal mechanism of dernatophytosis itch.

Footnotes

  • This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology, Japan [Grants-in-Aid for Young Scientists (B) 19790051, 22790063]; the Ministry of Education, Culture, Sports, Science and Technology, Japan [Grant-in-Aid for Scientific Research (B)23390153]; and the Health, Labor and Welfare Ministry, Japan. This work was also supported in part by the National BioResource Project in Japan (http://www.nbrp.jp/).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.112.195222.

  • ABBREVIATIONS:

    PAR
    proteinase-activated receptor
    ADV
    A. vanbreuseghemii
    FK888
    N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-l-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-l-alaninamide.

  • Received April 4, 2012.
  • Accepted July 2, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 343 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 343, Issue 1
1 Oct 2012
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Research ArticleInflammation, Immunopharmacology, and Asthma

Dermatophytes and Itch

Tsugunobu Andoh, Yusuke Takayama, Takako Yamakoshi, Jung-Bum Lee, Ayako Sano, Tadamichi Shimizu and Yasushi Kuraishi
Journal of Pharmacology and Experimental Therapeutics October 1, 2012, 343 (1) 91-96; DOI: https://doi.org/10.1124/jpet.112.195222

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Research ArticleInflammation, Immunopharmacology, and Asthma

Dermatophytes and Itch

Tsugunobu Andoh, Yusuke Takayama, Takako Yamakoshi, Jung-Bum Lee, Ayako Sano, Tadamichi Shimizu and Yasushi Kuraishi
Journal of Pharmacology and Experimental Therapeutics October 1, 2012, 343 (1) 91-96; DOI: https://doi.org/10.1124/jpet.112.195222
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