Coordinate expression of secretory phospholipase A₂ and cyclooxygenase- 2 in activated human keratinocytes

PGE₂ levels are altered in human epidermis after in vivo wounding; however, mechanisms modulating PGE₂ production in activated keratinocytes are unclear. In previous studies, we showed that PGE₂ is a growth-promoting autacoid in human primary keratinocyte cultures, and its production is modulated by plating density, suggesting that regulated PGE₂ synthesis is an important component of wound healing. Here, we examine the role of phospholipase A₂ (PLA₂) and cyclooxygenase (COX) enzymes in modulation of PGE₂ production. We report that the increased PGE₂ production that occurs in keratinocytes grown in nonconfluent conditions is also observed after in vitro wounding, indicating that similar mechanisms are involved. This increase was associated with coordinate upregulation of both COX-2 and secretory PLA₂ (sPLA₂) proteins. Increased sPLA₂ activity was also observed. By RT-PCR, we identified the presence of type IIA and type V sPLA₂, along with the M-type sPLA₂ receptor. Thus the coordinate expression of sPLA₂ and COX-2 may be responsible for the increased prostaglandin synthesis in activated keratinocytes during wound repair.