The differential role of prostaglandin E2 receptors EP3 and EP4 in regulation of fever.
The innate immune system of mammals is able to detect bacteria when they infect local tissue or enter the blood stream, and initiate an immediate immune response. Prostaglandin (PG) E2 is considered as the most important link between the peripheral immune system and the brain. Due to four PGE2 receptors (EP receptors) and their differential expression in various areas of the hypothalamus and brain stem, PGE2 mediates different components of the acute phase reaction. A fever model is discussed in which the preoptic area contains the mechanisms for both hyperthermic and hypothermic responses and EP receptors in the median preoptic area (MnPO) modulate the thermogenic system. The neuron-specific modulation of EP receptors in the MnPO can be critically tested by using Cre-recombinase-mediated DNA recombination in genetically engineered mice. A concept for mice with conditional expression of EP3R and EP4R to investigate the different roles of those receptors in lipopolysaccharide (LPS)-induced fever is presented.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. mlazarus@bidmc.harvard.edu
Michael
M
Lazarus
D000210:Acute-Phase Reaction / Q000503:physiopathology; D000818:Animals; D001933:Brain Stem / Q000737:chemistry / Q000503:physiopathology; D015232:Dinoprostone / Q000502:physiology*; D005334:Fever / Q000503:physiopathology*; D017353:Gene Deletion; D007031:Hypothalamus / Q000737:chemistry / Q000503:physiopathology; D007035:Hypothermia / Q000503:physiopathology; D019426:Integrases; D051379:Mice; D018345:Mice, Knockout; D011301:Preoptic Area / Q000737:chemistry / Q000503:physiopathology; D018078:Receptors, Prostaglandin E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
C545648:Ptger3 protein, mouse; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C045073:Cre recombinase; D019426:Integrases; D015232:Dinoprostone