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Published on: December 23, 2010
Involvement of leukotriene B4 in dermatophyte-related itch in mice
Tsugunobu Andoh1, Yusuke Takayama1, Yasushi Kuraishi1
1Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Japan.
Background:
Proteinase-activated receptor-2 (PAR2) is involved in dermatophyte-induced scratching and leukotriene B4 (LTB4) release from keratinocytes. We investigated whether PAR2-mediated LTB4 production is involved in dermatophyte-induced scratching.
Methods:
Dermatophyte extract was injected intradermally and scratching was observed in mice. LTB4 was determined by enzyme immunoassay.
Results:
Dermatophyte extract-induced scratching was inhibited by zileuton (5-lipoxygenase inhibitor), ONO-4057 (LTB4 antagonist), FSLLRY-NH2 (PAR2 antagonist), and anti-PAR2 antibody. Dermatophyte extract injection increased the cutaneous content of LTB4, which was inhibited by zileuton and FSLLRY-NH2.
Conclusion:
These results suggest the involvement of LTB4 in dermatophyte-associated itch. LTB4 production might be due to PAR2 stimulation in the skin.
Insights
Proteinase-activated receptor-2 (PAR2) activation leads to leukotriene B4 (LTB4) production, causing dermatophyte-induced scratching. Inhibiting PAR2 or LTB4 pathways effectively reduces this itch response in mice.
Area of Science:
- Dermatology
- Immunology
- Pharmacology
Background:
- Proteinase-activated receptor-2 (PAR2) plays a role in skin responses to dermatophytes, including scratching and leukotriene B4 (LTB4) release.
- Keratinocytes are a key source of LTB4 in the skin.
Purpose of the Study:
- To investigate the role of PAR2-mediated LTB4 production in dermatophyte-induced scratching.
- To determine if blocking PAR2 or LTB4 pathways can alleviate scratching.
Main Methods:
- Mice were injected intradermally with dermatophyte extract to induce scratching.
- LTB4 levels were quantified using enzyme immunoassay.
- Pharmacological inhibitors and antagonists (zileuton, ONO-4057, FSLLRY-NH2, anti-PAR2 antibody) were used to assess their effects on scratching and LTB4 production.
Main Results:
- Dermatophyte extract induced significant scratching behavior in mice.
- Scratching was significantly reduced by zileuton (5-lipoxygenase inhibitor), ONO-4057 (LTB4 antagonist), FSLLRY-NH2 (PAR2 antagonist), and anti-PAR2 antibody.
- Dermatophyte extract injection increased cutaneous LTB4 levels, which were suppressed by zileuton and FSLLRY-NH2.
Conclusions:
- LTB4 is implicated in the itch sensation associated with dermatophyte infections.
- PAR2 stimulation in the skin appears to be a primary mechanism for LTB4 production.
- Targeting the PAR2-LTB4 pathway offers a potential therapeutic strategy for dermatophyte-induced pruritus.
