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Published on: September 7, 2013
Possible involvement of keratinocyte-derived microvesicle particles in human photosensitivity disorders
Risha Annamraju1, Madison S Owens1, Anita Thyagarajan1
1Department of Pharmacology & Toxicology, Wright State University, Boonshoft School of Medicine, Dayton OH.
Background:
Previous murine studies have implicated acid sphingomyelinase-(aSMase) generated subcellular microvesicle particles (MVP) in photosensitivity.
Objective:
The current double-blinded placebo-controlled studies examined if a single localized ultraviolet B radiation (UVB) treatment generated more MVP in human subjects with self-identified photosensitivity versus normal controls. A topical 4% formulation of the aSMase inhibitor imipramine applied immediately after UVB blocked the MVP release and erythema responses. Erythema responses at 24 and 72 h in response to multiple UVB fluences and minimal erythema doses (MED) at 24 h and effects of imipramine were also tested.
Results:
Small cohorts of 10 adult self-identified photosensitive subjects and 10 controls were enrolled in these pilot studies which revealed increased levels of skin MVP in UVB-treated photosensitive subjects over controls which correlated with MED values. Moreover, post-UVB application of imipramine blunted UVB-induced MVP responses as well as tended to diminish erythema levels at 4 h but not at 24- or 72 h in photosensitive patients.
Conclusion:
Though limited by low numbers of self-identified subjects, these pilot studies provide some support for the hypothesis that MVP could be involved in multiple types of human photosensitivity responses and suggest aSMase inhibition as a potential therapeutic strategy.
Insights
Subcellular microvesicle particles (MVP) generated by acid sphingomyelinase (aSMase) are implicated in photosensitivity. Inhibiting aSMase with imipramine reduced MVP and erythema in human subjects, suggesting a potential therapeutic strategy.
Area of Science:
- Dermatology
- Biochemistry
- Photobiology
Background:
- Murine studies suggest acid sphingomyelinase (aSMase) generates microvesicle particles (MVP) involved in photosensitivity.
- MVP are subcellular particles released from cells.
Purpose of the Study:
- To investigate if ultraviolet B (UVB) radiation increases MVP in photosensitive human subjects compared to controls.
- To evaluate the effect of topical imipramine, an aSMase inhibitor, on UVB-induced MVP and erythema.
Main Methods:
- Double-blinded, placebo-controlled pilot study with 10 photosensitive subjects and 10 controls.
- Localized UVB treatment followed by topical imipramine application.
- Measurement of skin MVP levels and erythema responses at various time points.
Main Results:
- UVB treatment increased skin MVP in photosensitive subjects compared to controls, correlating with minimal erythema dose (MED).
- Imipramine application post-UVB reduced MVP release and tended to decrease early erythema in photosensitive patients.
- Erythema reduction by imipramine was not sustained at 24 or 72 hours.
Conclusions:
- Pilot data suggest MVP involvement in human photosensitivity.
- aSMase inhibition presents a potential therapeutic avenue for photosensitive conditions.
- Further research with larger cohorts is warranted.
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