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Am J Physiol Cell Physiol 278: C822-C833, 2000;
0363-6143/00 $5.00
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Vol. 278, Issue 4, C822-C833, April 2000

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

Krystyna E. Rys-Sikora1, Raymond L. Konger1, John W. Schoggins1, Rama Malaviya2, and Alice P. Pentland1

1 Department of Dermatology, University of Rochester Medical Center, Rochester, New York 14642; and 2 Drug Discovery Enterprises, Hughes Institute, St. Louis, Missouri 55113

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.

wound healing; primary human keratinocytes; arachidonic acid; prostaglandin E2; secretory phospholipase A2 receptor


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