Coordinate expression of secretory phospholipase A(2) and cyclooxygenase-2in activated human keratinocytes

PGE(2) levels are altered in human epidermis after in vivo wounding; howeve r, mechanisms modulating PGE(2) production in activated keratinocytes are u nclear. In previous studies, we showed that PGE(2) is a growth-promoting au tacoid in human primary keratinocyte cultures, and its production is modula ted by plating density, suggesting that regulated PGE(2) synthesis is an im portant component of wound healing. Here, we examine the role of phospholip aseA(2) (PLA(2)), and cyclooxygenase (COX) enzymes in modulation of PGE(2) production. We report that the increased PGE(2) production that occurs in k eratinocytes grown in nonconfluent conditions is also observed after in vit ro wounding, indicating that similar mechanisms are involved. This increase was associated with coordinate upregulation of both COX-2 and secretory PL A(2) (sPLA(2)) proteins. Increased sPLA(2) activity was also obsened. By RT -PCR, we identified the presence of type IIA and type V sPLA(2), along with the M-typee sPLA(2) receptor. Thus the coordinate expression of sPLA(2) an d COX-2 may be responsible far the increased prostaglandin synthesis in act ivated keratinocytes during wound repair.