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*
Center for Experimental Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
Wistar Institute, Philadelphia, PA 19104;
Department of Pharmacology, Catholic University School of Medicine, Rome, Italy; and
§
Department of Medicine and Aging, University of Chieti "G. D’Annunzio" School of Medicine, Chieti, Italy
Prostaglandins (PGs) are lipid-derived mediators of rapid and
localized cellular responses. Given the role of PG in supporting thymic
T cell development, we investigated the expression of the PG synthases,
also known as cyclooxygenases (COX)-1 and -2, in the biosynthesis of
PGs in thymic stromal cell lines. The predominant isozyme expressed in
cortical thymic epithelial cells was COX-1, while COX-2 predominated in
the medulla. IFN-
up-regulated expression and activity of COX-2 in
medullary cells, in which COX-2 was expressed constitutively. In
contrast, IFN- down-regulated COX-1 activity, but not expression, in
cortical cells. Stromal cells support T cell development in the thymus,
although the mediators of this effect are unknown. Selective inhibition
of COX-2, but not COX-1, blocked the adhesion of
CD4+CD8+ and CD4+CD8-
thymocytes to medullary cell lines. No effect of the inhibitors was
observed on the interactions of thymocytes with cortical epithelial
lines. These data further support the differential regulation of COX-1
and COX-2 expression and function in thymic stromal cells. PGs produced
by COX-2 in the medullary thymic stroma may regulate the development of
thymocytes by modulating their interaction with stromal
cells.
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