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Prostanoids and inflammation: a new concept arising from receptor knockout mice

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Abstract

Prostanoids including various types of prostaglandins and thromboxanes are arachidonate metabolites produced and released in response to a variety of physiological and pathological stimuli and function to maintain the body homeostasis. Since cyclooxygenase, the enzyme initiating their biosynthesis, is inhibited by aspirin-like antipyretic, anti-inflammatory, and analgesic drugs, contribution of prostanoids to acute inflammation such as fever generation, pain sensitization, and inflammatory swelling has been recognized very early. On the other hand, since aspirin-like drugs generally show little effects on allergy and immunity, it has been believed that prostanoids play little roles in these processes. Prostanoids act on a family of G-protein-coupled receptors designated PGD receptor, PGE receptor subtypes EP1–EP4, PGF receptor, PGI receptor, and TX receptor to elicit their actions. Studies using mice deficient in each of these receptors have revealed that prostanoids indeed function in the above aspirin-sensitive processes. However, these studies have also revealed that prostanoids exert both pro-inflammatory and anti-inflammatory actions not only by acting as mediators of acute inflammation but also by regulating gene expression in mesenchymal and epithelial cells at inflammatory site. Such dual actions of prostanoids are frequently seen in immune and allergic reactions, where different type of prostanoids and their receptors often exert opposite actions in a single process. Thus, a new concept on the role of prostanoids in inflammation has arisen from studies using the receptor knockout mice.

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Conflict of interest statement

The author declares that his research on prostanoid receptors has been supported in part by Ono Pharmaceuticals Co. Ltd. through collaboration with Kyoto University. Ono Pharmaceuticals Co. Ltd. has developed compounds discussed in this manuscript.

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  1. Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan

    Shuh Narumiya

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Correspondence to Shuh Narumiya.

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Narumiya, S. Prostanoids and inflammation: a new concept arising from receptor knockout mice. J Mol Med 87, 1015–1022 (2009). https://doi.org/10.1007/s00109-009-0500-1

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