Role of Stratum Corneum Ceramide in Water and Barrier Functions: Implication to Pathogenesis of Atopic Dermatitis

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 nonlesional
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) Abnormality in Cutaneous Permeability
Barrier Function, 2) Is Barrier Disruption a Cause or a Result of Dermatitis?,3) Is Barrier Abnormality
Inherent or not?, 4) Filaggrin Mutation and Barrier Disruption, 5) Contribution of Barrier Abnormality to
Th1/Th2 Balance, 6) Role of Ceramides, 7) Th1/Th2 Balance and Ceramide Deficiency, 8) S. Aureus
colonization and Ceramide Deficiency, 9) Is Ceramide Deficiency Inherent or not ?, 10) Inflammation
as a Causative Factor to Down-Regulate Ceramide Generation, 11) Biological Mechanisms
Underlying Ceramide Deficiency, 12) Clinical Efficacy of Ceramide as a Major Role for the
Pathogenesis of AD