Distinct expression of cyclooxygenase-1 and -2 in the human thymus

Abstract

Cyclooxygenase (COX)‐1 and ‐2 catalyze the formation of prostaglandins (PG). Given the role of COX and PG during intrathymic T cell development in the mouse, we investigated the expression andlocalization of these isozymes in the human thymus. mRNA and proteins correspondent to COX‐1 and ‐2 were observed from whole thymus extracts. By immunohistochemistry, COX‐2 was selectively localized in the medulla and it was predominant in a subset of stromal cells. By contrast, COX‐1 was diffusely and exclusively present in the cortex, both in thymocytes at early stages of differentiation and in cytokeratin‐positive epithelial cells, as demonstrated by double immunostaining and flow cytometry analysis. COX‐2‐positive cells in the medulla expressed cytokeratin and HLA‐DR molecules, but they were negative for dendritic or macrophagic antigens. In addition, COX‐2‐positive cells expressed both the epidermal growth factor receptor and its ligand, the transforming growth factor‐α. The inducible isoform of the PGE2 synthase was also present in the same cells, while was absent from COX‐1‐expressing cells of the cortex. Finally, electron microscopy confirmed that COX‐2 was mainly localized in the cytoplasm of cytokeratin‐positive cells, along the rough endoplasmic reticulum. In conclusion, COX‐2 and the inducible isoform of PGE2 synthase appear to be constitutively and selectively present in medullary epithelial cells of the human thymus, whereas COX‐1 is predominantly present in the thymic cortex, both in the stroma and in developing thymocytes.

Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation

“…For AA loading experiments, washed cells were incubated with HBSS/0.1% BSA/10 mM AA (Cayman Chemical), and supernatants were collected. 2,4 For dose/response experiments with inhibitors, cells were preincubated with HBSS/BSA containing various concentrations of drugs and then 10 mM AA were added. PGE 2 and TXB 2 were measured in cell supernatants using previously validated RIA.…”

“…1 In spite of structural and functional homologies, COX-1 and -2 are encoded by different genes and subserve distinct functions: COX-1 is the constitutive isoform, 1 while COX-2 is largely inducible. 1 However, this paradigm has many exceptions: COX-1 can be regulated during lymphoid maturation, 2,3 while COX-2 is stably expressed in the brain, reproductive tissues, kidney and thymus. 1 Circulating leukocytes diversely express COX isoforms: activated granulocytes and monocytes upregulate COX-2, releasing PGE 2 and TXA 2 .…”

“…1 Circulating leukocytes diversely express COX isoforms: activated granulocytes and monocytes upregulate COX-2, releasing PGE 2 and TXA 2 . 3 Increasing evidence suggests a role for COX and prostanoids in hematopoiesis: CD34 þ stem cells express COX-1 and synthesize PGE 2 . 4 Prostaglandins participate to the intrathymic development of mouse and possibly human T cells.…”

“…4 Prostaglandins participate to the intrathymic development of mouse and possibly human T cells. 2,3 Metabolically active COX-1 and -2 are expressed during human megakaryopoiesis. 4 PGE 2 enhances hemoglobinization of erythroid cells.…”

A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation

“…10 Consistent with these reports, expression of various prostaglandin biosynthetic enzymes and receptors has been detected in the thymus. 11 Dendritic cells (DCs) are considered to be the only antigenpresenting cell (APC) capable of priming naive T cells, and they are also potent stimulators of recall responses. 12 Briefly, DCs exist in the periphery as immature cells where they serve as "sentinels," responsible for capturing antigen.…”