Ceramides are the most abundant lipids constituting the intercellular matri
x of the skin stratum corneum and their critical role in skin homeostasis h
as been extensively documented. Their concentration in the skin highly depe
nds on the rate of availability of the enzymes involved in ceramide generat
ion. The aim of this study was to investigate whether the concentration of
prosaposin was altered in the skin of patients with psoriasis vulgaris. Pro
saposin, the precursor of saposins (sphingolipid activator proteins), was m
easured in lesional and nonlesional skin of psoriatic patients and in norma
l skin from surgical patients, both at the mRNA and at the protein level. D
ensitometric analysis of reverse transcriptase-polymerase chain reaction ba
nds separated by gel-electrophoresis showed a progressive decrease of prosa
posin mRNA expression in nonlesional and lesional psoriatic skin, being sub
stantially decreased in lesional psoriatic skin compared with normal contro
l skin. Immunohistochemical analysis showed a significant decrease of prosa
posin level in the stratum corneum of psoriatic lesional skin (both in acti
ve-type and in chronic-type plaque) compared with nonlesional and with norm
al skin (p < 0.01), and in psoriatic nonlesional skin compared with normal
control (p < 0.05). Immunolocalization of sphingomyelinase in lesional and
nonlesional psoriatic skin showed a decrease in the level of this enzyme in
the stratum corneum of psoriatic lesional, compared with nonlesional skin.
These results support the concept that disturbance of epidermal barrier fu
nction caused by derangement in ceramide generation can be crucial for the
development of psoriatic skin diseases.