Abstract
Prostaglandin G and H synthases, or cyclooxygenases (COXs), catalyze the formation of prostaglandins (PGs). Whereas COX-1 is diffusely expressed in lymphoid cells in embryonic day 15.5 thymus, COX-2 expression is sparse, apparently limited to stromal cells. By contrast, COX-2 is predominant in a subset of medullary stromal cells in three- to five-week-old mice. The isozymes also differ in their contributions to lymphocyte development. Thus, experiments with selective COX-1 inhibitors in thymic lobes from normal and recombinase-activating gene-1 knockout mice support a role for this isoform in the transition from CD4(-)CD8(-) double-negative (DN) to CD4(+)CD8(+) double-positive (DP). Concordant data were obtained in COX-1 knockouts. Pharmacological inhibition and genetic deletion of COX-2, by contrast, support its role during early thymocyte proliferation and differentiation and, later, during maturation of the CD4 helper T-cell lineage. PGE2, but not other PGs, can rescue the effects of inhibition of either isoform, although it acts through distinct EP receptor subtypes. COX-dependent PG generation may represent a mechanism of thymic stromal support for T-cell development.
Lingua originale | English |
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pagine (da-a) | 1469-1477 |
Numero di pagine | 9 |
Rivista | THE JOURNAL OF CLINICAL INVESTIGATION |
Volume | 103 |
DOI | |
Stato di pubblicazione | Pubblicato - 1999 |
Keywords
- Animals
- Antigens, CD4
- Antigens, CD8
- Base Sequence
- Cell Differentiation
- Cyclooxygenase 1
- Cyclooxygenase 2
- Cyclooxygenase 2 Inhibitors
- Cyclooxygenase Inhibitors
- DNA Primers
- Dinoprostone
- Gene Expression
- Genes, RAG-1
- Isoenzymes
- Membrane Proteins
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Models, Biological
- Prostaglandin-Endoperoxide Synthases
- T-Lymphocytes