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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, Ohio, USA.
Abstract:
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. Small cohorts of 10 adult self-identified photosensitive subjects and 12 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. 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) play a role in human photosensitivity. Inhibiting acid sphingomyelinase (aSMase) with imipramine reduced MVP release and erythema after UVB exposure in pilot studies.
Area of Science:
- Dermatology
- Biochemistry
- Photobiology
Background:
- Previous murine studies suggest acid sphingomyelinase (aSMase)-generated microvesicle particles (MVP) contribute to photosensitivity.
- Human photosensitivity mechanisms, particularly the role of subcellular particles, require further investigation.
Purpose of the Study:
- To investigate if ultraviolet B (UVB) radiation generates more MVP in photosensitive individuals compared to controls.
- To evaluate the efficacy of topical imipramine, an aSMase inhibitor, in blocking UVB-induced MVP release and erythema.
Main Methods:
- Double-blinded, placebo-controlled pilot studies involving self-identified photosensitive subjects and normal controls.
- Localized UVB treatment followed by immediate topical application of 4% imipramine or placebo.
- Quantification of skin MVP levels and assessment of erythema responses at various time points and UVB fluences.
Main Results:
- UVB-treated photosensitive subjects exhibited higher skin MVP levels than controls, correlating with minimal erythema doses (MED).
- Imipramine application post-UVB inhibited MVP release and tended to reduce erythema at 4 hours, but not at 24 or 72 hours.
- Pilot study findings suggest MVP involvement in human photosensitivity.
Conclusions:
- Microvesicle particles (MVP) may be implicated in various human photosensitivity conditions.
- Inhibition of acid sphingomyelinase (aSMase) presents a potential therapeutic avenue for managing photosensitivity.
- Further research with larger cohorts is warranted to confirm these findings.
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