Role of Ceramide in the Barrier Function of the Stratum Corneum, Implications for the Pathogenesis of Atopic Dermatitis

Abstract

Atopic dermatitis is a recurrent dermatitis which is characterized clinically by atopic dry skin and functionally by cutaneous barrier disruption even in the non-lesional skin. These abnormalities have been thought to be mainly attributable to significantly decreased levels of ceramides even in the non-lesional stratum corneum. Recently, in association with the barrier disruption in atopic dermatitis skin, prevalent and rare loss-of-function mutations in the gene encoding filaggrin have been reported to be an important pre-disposing factor for the development of atopic dermatitis. However, a mechanistic connection between filaggrin loss-of-function mutations and barrier disruption has not been resolved and remains controversial. This review article explores the physiological and biochemical basis for the atopic dermatitis phenotype in terms of the barrier abnormality and associated factors such as ceramides and its metabolites in the following sequence: (1) Clinical characteristics as a recurrent dermatitis (2) Abnormality in cutaneous permeability barrier function (3) Is barrier disruption a cause or a result of dermatitis? (4) Is the barrier abnormality inherent or not? (5) Role of ceramides (6) Transglutaminase or filaggrin mutations and barrier disruption (7) Contribution of the barrier abnormality to the Th1/Th2 balance (8) Th1/Th2 balance and ceramide deficiency (9) S. aureus colonization and ceramide deficiency (10) Is the ceramide deficiency inherent or not? (11) Inflammation as a causative factor that downregulates ceramide generation, (12) Biological mechanisms underlying the ceramide deficiency (13) Clinical efficacy of ceramide as a major role for the pathogenesis of atopic dermatitis