Prostaglandin E2 enhancement of interferon-gamma production by antigen-stimulated type 1 helper T cells.
Prostaglandin E2 (PGE2) is a potent mediator generated in immune tissues by cyclooxygenation of arachidonic acid. PGE2 affects T cell functions through four homologous G protein-coupled receptors termed EP1R, EP2R, EP3R, and EP4R that differ in tissue distribution and signaling. Antigen-evoked secretion of interferon-gamma (IFN-gamma) by sperm whale myoglobin-specific Th1 cells of DBA/2 mouse I-Ed-restricted clones, that express EP3Rs and EP4Rs, was enhanced a maximum of 3-fold by 10(-10) to 10(-8) M PGE2 and 2.5-fold each for the EP1R/EP3R-directed agonist sulprostone (10(-8) and 10(-7) M) and for the EP4R/EP3R/EP2R agonist misoprostol (10(-9) M). Neither PGE2 nor the synthetic analogs affected secretion of IFN-gamma by PMA plus ionomycin-stimulated clones of Th1 cells. Antigen-evoked secretion of IFN-gamma by influenza hemagglutinin-specific mouse lymph node Th1 cells, that also express EP3Rs and EP4Rs, was increased a maximum of 12-fold by 10(-9) to 10(-8) M PGE2, 14-fold by 10(-9) M sulprostone, and 10-fold by 10(-9) M misoprostol. Production of IFN-gamma by either type of Th1 cell was not affected significantly by 10(-6) M PGE2 alone. The generation of IFN-gamma by antigen-stimulated Th1 cells thus is significantly enhanced by physiologically relevant concentrations of PGE2.
Bloom
D
D
Departments of Medicine and Microbiology-Immunology, University of California Medical Center, San Francisco, California, 94143-0711, USA.
Jabrane-Ferrat
N
N
Zeng
L
L
Wu
A
A
Li
L
L
Lo
D
D
Turck
C W
CW
An
S
S
Goetzl
E J
EJ
D000818:Animals; D000941:Antigens / Q000276:immunology; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D016595:Misoprostol / Q000378:metabolism / Q000494:pharmacology; D009211:Myoglobin / Q000138:chemical synthesis / Q000276:immunology; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D009211:Myoglobin; C545636:Ptger1 protein, mouse; C545645:Ptger2 protein, mouse; C545648:Ptger3 protein, mouse; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D016595:Misoprostol; C016767:sulprostone; D007371:Interferon-gamma; D015232:Dinoprostone