A decrease in ceramide in the
stratum corneum causes water loss and barrier dysfunction
in the epidermis, including a loss of protection
against antigens and bacteria (Mizutani et al. 2009). In
addition, the reduction in the stratum corneum ceramide
levels has been proposed as a possible aetiological factor
in atopic dermatitis, psoriasis, contact dermatitis and irritant
dermatitis (Motta et al. 1994; Murata et al. 1996;
Berardesca et al. 2001).
Sphingomyelinase is localized in the epidermal lamellar
bodies and stratum corneum interstices and has been
classified as acid, alkaline and neutral SMase based on
their pH optima. Acid SMase is a soluble glycoprotein
with an optimum activity at pH 5. The absence of this
enzyme in humans is known to lead to neurological disorder
Niemann–Pick syndrome. It has been reported that
patients with Niemann–Pick syndrome also displayed an
abnormality in skin permeability barrier homeostasis with
delayed recovery kinetics following acute barrier disruption
(Schmuth et al. 2000). Considering that acid SMase
is located in the outer epidermis, it is thus responsible
for the generation of ceramides for basal permeability
barrier functions (Jensen et al. 2005). In addition, a
decrease in inner epidermal acid SMase has been associated
with skin ageing (Jensen et al. 2005). Neutral SMase
on the other hand is cell membrane associated and is
important for cell signalling during permeability barrier
repair via enhanced accumulation of ceramide (Kreder
et al. 1999). Decreased neutral SMase activity in the outer
as well as in the inner epidermal layers has been found in
aged skin (Jensen et al. 2005), possibly attributed to
reduced proliferation rate, leading to reduced capacity for
barrier repair. Mice defective in TNF-induced neutral
SMase activation showed reduced capacity of barrier
repair and smaller increase in epidermal proliferation
upon barrier disruption (Kreder et al. 1999). Neutral
SMase activity was also reported to be reduced in lesional
and nonlesional atopic dermatitis skin, correlating with
impaired expression of cornified envelope proteins and
keratins, which is important for skin barrier functions