Prostanoids in immunity: roles revealed by mice deficient in their receptors.
Prostanoids including prostaglandins (PGs) and thromboxanes (TX) are a group of lipid mediators formed and released in response to various, often noxious, stimuli. While the roles of prostanoids in acute inflammatory responses are well known and have been extensively studied, it is generally believed that they play very little in immunity. This is partly because non-steroidal anti-inflammatory drugs that inhibit prostanoid synthesis have little effects on immune processes in vivo. Prostanoids exert their actions by acting on a family of G-protein-coupled receptors. They include PGD receptor, EP1, EP2, EP3 and EP4 subtypes of PGE receptor, PGF receptor, PGI receptor and TX receptor. We generated mice deficient in each of these prostanoid receptors individually, and examined their roles under various pathological conditions. These studies have revealed that prostanoids works at various sites or levels of immune responses and exert many, often opposing, actions. For example, using EP4-deficient mice, we found that stimulation of the PGE(2)-EP4 signaling in dendritic cells facilitates their migration and maturation, while the stimulation of the same pathway in T cells potently suppresses their activation and proliferation. The latter action is evident in PGE(2)-mediated suppression of T cell proliferation in the gut of mice subjected to dextran sodium sulfate-induced colitis, a model of inflammatory bowel disease. Here I summarize our findings obtained by these and other studies. These findings suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of certain immunological disorders.
Narumiya
Shuh
S
Department of Pharmacology, Kyoto University Faculty of Medicine, Yoshida, Sakyo-ku, 606-8501, Kyoto, Japan. snaru@mfour.med.kyoto-u.ac.jp
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D007109:Immunity / Q000502:physiology*; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D011453:Prostaglandins / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000235:genetics; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012867:Skin / Q000276:immunology; D013928:Thromboxane A2 / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D011453:Prostaglandins; C545651:Ptger4 protein, mouse; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013928:Thromboxane A2