[Inflammation-allergy and prostanoids. (1). Prostanoids in experimental inflammatory reaction].
It is known that prostaglandins (PGs) modify the inflammatory reaction in concert with other biologically active mediators. However, characteristics of these interactions or modulating actions have not yet been clarified well. Recently, the production of mice with specific receptor deficiencies by using the gene targeting procedure for PG receptors has accelerated elucidation of the roles of PGs through correlation of their phenotypes and experimental features. Here I discuss roles of PGs in experimental paw edema, the writhing reaction of a pain model, and regulation of cytokine production, as determined using some PG-receptor-deficient mice. From the experiment of carrageenin-induced paw edema in IP receptor-deficient mice, with an indomethacin or bradykinin antagonist, we conclude that bradykinin initially induces paw swelling and then stimulates the release PGI2, which in turn enhances the swelling with bradykinin. By comparing the writhing responses in IP-deficient and wild-type mice, we found that PGI2 is a main mediator for this pain reaction. However, in the LPS-pretreated mice, not only PGI2 but also other PGs produced by COX-2 may be involved in pain induction. Production of TNF alpha and IL-10 was modified with PGI2 or PGE2; the production of TNF alpha was down-regulated by the stimulation via IP-, EP2- or EP4 receptor, but that of IL-10 was up-regulated by these receptors, resulting in an anti-inflammatory effect.
Ueno
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A
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Japan.
OhIshi
S
S
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007249:Inflammation / Q000209:etiology*; D018836:Inflammation Mediators / Q000502:physiology*; D010146:Pain / Q000209:etiology; D011453:Prostaglandins / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D011453:Prostaglandins; D011982:Receptors, Prostaglandin