Differential expression and regulation of cyclooxygenase isozymes in thymic stromal cells

B Rocca, LM Spain, G Ciabattoni, C Patrono… - The Journal of …, 1999 - journals.aai.org
B Rocca, LM Spain, G Ciabattoni, C Patrono, GA FitzGerald
The Journal of Immunology, 1999journals.aai.org
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-γ
up-regulated expression and activity of COX-2 in medullary cells, in which COX-2 was …
Abstract
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-γ up-regulated expression and activity of COX-2 in medullary cells, in which COX-2 was expressed constitutively. In contrast, IFN-γ 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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