Distinct expression of cyclooxygenase-1 and -2 in the human thymus.
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 and localization 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-alpha. The inducible isoform of the PGE(2) 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 PGE(2) 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.
Rocca
Bianca
B
Department of Internal Medicine, Catholic University School of Medicine, Rome, Italy. b.rocca@tiscali.it
Maggiano
Nicola
N
Habib
Aida
A
Petrucci
Giovanna
G
Gessi
Marco
M
Fattorossi
Andrea
A
Lauriola
Libero
L
Landolfi
Raffaele
R
Ranelletti
Franco O
FO
D002648:Child; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D066246:ErbB Receptors / Q000378:metabolism; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism; D008565:Membrane Proteins; D016253:Microscopy, Immunoelectron; D010641:Phenotype; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000033:anatomy & histology / Q000201:enzymology* / Q000276:immunology; D014018:Tissue Distribution; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D006684:HLA-DR Antigens; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D007633:Keratins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases