The Pleiotropic Action of PGE2: Phenotypes of EP Knockout Mice
Genetic deletion | Inflammation/Immunity | Carcinogenesis | Reproduction | Kidney | Lung | Central or peripheral nervous system | Bone | Gastro- intestinal tract |
---|---|---|---|---|---|---|---|---|
Numbers in parentheses indicate references. MLR, mixed lymphoid reaction; AOM, azoxymethane; NMDA, N-Methyl-D-Aspartate; PTH, parathyroid hormone. | ||||||||
↓ indicates reduction; ↑ indicates enhancement. | ||||||||
EP1−/ − | No effect on MLR (10) | ↓ Early and AOM-induced colon cancer (24) | ↓ Airway responsiveness (27) | ↓ Inflammationdependent fever (26) ↓ NMDA- induced stroke (28) | ↓ Gastric mucosal integrity (25) | |||
EP2−/ − | ↓ PGE2-dependent MLR inhibition (10) | ↓ skin and colon tumors (12, 15) ↓ Tumor angiogenesis (13) ↓ Mammary gland hyperplasia (14) | ↓ Ovulation and fertilization (11) | ↓ Hypotensive effect of PGE2 (9) Saltsensitive hypertension (9) ↓ Renin secretion rate (9) | ↓ PGE2- induced bronchodilation (9) | ↓ Spinal PGE2-evoked hyperalgesia (16) ↑Stroke after artery occlusion or NMDA (17, 18) | ↓ Osteoclastogenic response to PGE2, PTH, and 1,25- OH Vitamin D3 (9) | |
EP3−/ − | ↑Allergic inflammation (21) No effect on MLR (10) | ↑Colon cancer development induced by AOM (22) | ↓ Capacity of urinary concentration (23) | ↓ Pyrogen-dependent fever (23) | No effect on gastric mucosal protection (25) Acid induced bicarbonate secretion from duodenum (23) | |||
EP4−/ − | ↓ Arthritis (9) ↓ PGE2-dependent MLR inhibition (10) ↓ Migration of APC cells (9) ↓ Skin hypersensitivity | ↓ Aberrant colic foci by AOM (9) | ↓ Renin secretion rate (9) | ↑Infarct in ischemiareperfusion injury (20) | ↓ Bone mass (9) ↓ Repair from fractures (19) | ↓ Intestine mucosal barrier (25) |