Characterization and differentiation-dependent regulation of secreted phospholipases A2 in human keratinocytes and in healthy and psoriatic human skin

Secreted phospholipases A(2) (sPLA(2)) expressed in the skin are thought to be involved in epidermal barrier homeostasis as well as in inflammation. We investigated the expression of the novel sPLA(2) subtypes in human skin at mRNA and protein levels in the epidermis and primary keratinocytes from healthy human skin, and in skin sections from patients with psoriasis, where the integrity of the epidermis is drastically affected. Immunofluorescence studies using specific antibodies for the different sPLA(2) enzymes show that sPLA(2)-IB, -IIF, and -X are predominantly expressed in suprabasal layers, whereas sPLA(2)-V and -IID are detected in the basal and spinous layers. sPLA(2)-IIA is weakly expressed, and sPLA(2)-IIE and XIIA are not detectable. Accordingly, in differentiated human primary keratinocyte cultures, the expression of sPLA(2)-IB, -IIF and -X was increased, whereas that of sPLA(2)-V and -IID was markedly decreased. In psoriatic skin, sPLA(2)-X was dramatically downregulated in the epidermis, whereas increased amounts of this enzyme together with sPLA(2)-IIA, -IID, and -IB appeared in the dermis. An enhanced release of these enzymes with the exception of sPLA(2)-IID was also observed after treatment of HaCaT keratinocytes with tumor necrosis factor-alpha/interferon-gamma. Treatment of HaCaT cells with sPLA(2)-X and -IB resulted in an increase in prostaglandin E-2 formation, suggesting a proinflammatory role of these enzymes during psoriasis. sPLA(2)-V completely disappeared. The differential locations of the sPLA(2) enzymes propose distinct roles of individual enzymes in skin.