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Mechanism of mustard oil-induced skin inflammation in mice
Abstract:
We examined the mechanism of the inflammatory response induced by topical application of mustard oil (0.5-20.0%/20 microliters per ear) to the mouse ear compared to that of the response to capsaicin. The dose-dependent increases in plasma extravasation and ear thickness reached a maximum at approximately 30 min after mustard oil application. Topical pretreatment of ears with capsaicin (250 micrograms/ear) diminished mustard oil-induced plasma extravasation for up to day 7 but not at day 14 after treatment. However, desensitization of the exudative response was not evoked by reapplication of mustard oil to ears. The inflammatory response to mustard oil did not differ between the ears of mast cell-deficient mice and those of the congenic normal mice. Mustard oil-induced plasma extravasation was unaffected by pretreatment with histamine H1 and 5-HT2 receptor antagonists and the capsaicin-functional inhibitor, ruthenium red, which inhibit capsaicin-induced ear oedema. The endopeptidase inhibitor, phosphoramidon, enhanced the ability of mustard oil to increase dye leakage. The tachykinin NK1 receptor antagonist, SR 140333 ((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)pi peridin-3-yl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2.]octane, chloride), not only inhibited mustard oil-induced plasma extravasation but also blocked the enhancement by phosphoramidon of the response to mustard oil. In contrast, the tachykinin NK2 receptor antagonist, SR 48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4,- dichlorophenyl)butyl]benzamide), and the tachykinin NK3 receptor antagonist, SR 142801 ((S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)pro pyl)-4- phenylpiperidin-4-yl)-N-methylacetamide), had no effect on plasma extravasation. The present results demonstrated that mustard oil induces mouse skin inflammation through a mechanism different from that for capsaicin. Mediators such as histamine and 5-HT from mast cells appear to be minor factors in the response to mustard oil. In addition, evidence supports the assumption that the tachykinin NK1 receptor is involved in this model.
Insights
Mustard oil induces skin inflammation via a distinct mechanism from capsaicin, involving the tachykinin NK1 receptor. This inflammatory response is not mediated by histamine or serotonin from mast cells.
Area of Science:
- Immunology
- Pharmacology
- Dermatology
Background:
- Topical application of irritants like mustard oil and capsaicin triggers inflammatory responses in the skin.
- Understanding the specific mechanisms of these responses is crucial for developing targeted treatments.
Purpose of the Study:
- To elucidate the inflammatory mechanism induced by topical mustard oil application in mouse ears.
- To compare this mechanism with that of capsaicin-induced inflammation.
- To identify key mediators and receptors involved in mustard oil-induced inflammation.
Main Methods:
- Mustard oil and capsaicin were applied topically to mouse ears to assess plasma extravasation and ear thickness.
- Experiments involved varying doses, pre-treatment with capsaicin, and utilizing mast cell-deficient mice.
- Pharmacological inhibitors targeting histamine H1, 5-HT2 receptors, capsaicin pathways, and tachykinin receptors (NK1, NK2, NK3) were employed.
- The role of endopeptidases was investigated using phosphoramidon.
Main Results:
- Mustard oil induced a dose-dependent increase in plasma extravasation and ear thickness, peaking around 30 minutes.
- Capsaicin pre-treatment desensitized the response to mustard oil for up to 7 days, but not 14 days.
- The inflammatory response to mustard oil was similar in mast cell-deficient and normal mice, suggesting minor roles for histamine and 5-HT.
- Tachykinin NK1 receptor antagonist SR 140333 inhibited mustard oil-induced plasma extravasation, while NK2 and NK3 antagonists had no effect.
- Phosphoramidon enhanced mustard oil-induced dye leakage, an effect blocked by SR 140333.
Conclusions:
- Mustard oil induces mouse skin inflammation through a mechanism distinct from capsaicin.
- Histamine and 5-HT released from mast cells are minor contributors to mustard oil-induced inflammation.
- The tachykinin NK1 receptor plays a significant role in mediating the inflammatory response to mustard oil.