Exploring the Impact of Ceramide Synthesis Enzymes on Atopic Dermatitis Severity
Session Number
MEDH 14
Advisor(s)
Amy S. Paller, MD, MS
Nihal Kaplan, Northwestern University, Feinberg School of Medicine, Department of Dermatology
Discipline
Medical and Health Sciences
Start Date
17-4-2024 10:25 AM
End Date
17-4-2024 10:40 AM
Abstract
Atopic dermatitis (AD; eczema) is a chronic skin disorder characterized by inflammation, itching, and compromised skin barrier function. Pathogenesis involves genetic factors, immune dysregulation, and skin barrier ceramide alterations. This research project explores the relationship between the ceramide de novo pathway and AD severity. Severity was determined serially based on assessing erythema, scaling, edema, and erosion using a 12-point scale (each 0-3) in a mouse model of AD induced by MC903 application on the ear. Ear samples were collected on challenge days 1, 4, and 9. RNA was extracted for quantitative real-time PCR to assess changes in biomarkers.
Maximum severity was reached at 4 days in terms of the clinical severity scale and cytokine changes. As found in human AD, expression of Sptlc3, encoding a key enzyme in de novo ceramide synthesis in differentiated skin, was significantly reduced in control mouse skin treated to induce AD. However, mice with the knockout of Sptlc3 did not develop AD spontaneously and, when treated topically with MC903, did not show increased AD severity or skewing of cytokines. These results suggest that other factors involved in de novo ceramide synthesis can compensate for the reduction in Sptlc3 in mouse skin, which deserves further exploration.
Exploring the Impact of Ceramide Synthesis Enzymes on Atopic Dermatitis Severity
Atopic dermatitis (AD; eczema) is a chronic skin disorder characterized by inflammation, itching, and compromised skin barrier function. Pathogenesis involves genetic factors, immune dysregulation, and skin barrier ceramide alterations. This research project explores the relationship between the ceramide de novo pathway and AD severity. Severity was determined serially based on assessing erythema, scaling, edema, and erosion using a 12-point scale (each 0-3) in a mouse model of AD induced by MC903 application on the ear. Ear samples were collected on challenge days 1, 4, and 9. RNA was extracted for quantitative real-time PCR to assess changes in biomarkers.
Maximum severity was reached at 4 days in terms of the clinical severity scale and cytokine changes. As found in human AD, expression of Sptlc3, encoding a key enzyme in de novo ceramide synthesis in differentiated skin, was significantly reduced in control mouse skin treated to induce AD. However, mice with the knockout of Sptlc3 did not develop AD spontaneously and, when treated topically with MC903, did not show increased AD severity or skewing of cytokines. These results suggest that other factors involved in de novo ceramide synthesis can compensate for the reduction in Sptlc3 in mouse skin, which deserves further exploration.