In involved psoriatic tissue, which is characterized by chronic
inflammation in both epidermis and dermis, elevated levels of
arachidonic acid and
eicosanoids have been measured. This implies that a
phospholipase A2 (PLA2) may be involved in the pathogenesis of
psoriasis. The PLA2's are a group of
enzymes that release
unsaturated fatty acids from the sn2-position of membrane
phospholipids. Once released, the
fatty acids are converted by various
enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of
eicosanoids such as
prostaglandins,
thromboxanes,
leukotrienes, and lipoxines.
Eicosanoids are important in a variety of physiological processes and play a central role in inflammatory mediators, such as
lyso-PAF (a precursor for PAF) and other
lysophospholipids, may also be formed through the action of a PLA2. We report for the first time the detection of transcripts of nonpancreatic
phospholipase A2 (npPLA2, type II) and cytosolic (c) PLA2 in human skin, and overexpression of npPLA2 in involved skin from patients with
psoriasis (plaque
psoriasis and pustular
psoriasis). Limited amounts of npPLA2
enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA2 than normal skin. Positive cells in dermis showed significantly higher levels of npPLA2 than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA2
enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in
eicosanoid overproduction in psoriatic tissue, and the npPLA2 may also be involved in potentiating cell activation, especially T cells.