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Prostaglandin-cytokine crosstalk in chronic inflammation.

ABSTRACT: Chronic inflammation underlies various debilitating disorders including autoimmune, neurodegenerative, vascular and metabolic diseases as well as cancer, where aberrant activation of the innate and acquired immune systems is frequently seen. Since non-steroidal anti-inflammatory drugs exert their effects by inhibiting COX and suppressing PG biosynthesis, PGs have been traditionally thought to function mostly as mediators of acute inflammation. However, an inducible COX isoform, COX-2, is often highly expressed in tissues of the chronic disorders, suggesting an as yet unidentified role of PGs in chronic inflammation. Recent studies have shown that in addition to their short-lived actions in acute inflammation, PGs crosstalk with cytokines and amplify the cytokine actions on various types of inflammatory cells and drive pathogenic conversion of these cells by critically regulating their gene expression. One mode of such PG-mediated amplification is to induce the expression of relevant cytokine receptors, which is typically observed in Th1 cell differentiation and Th17 cell expansion, events leading to chronic immune inflammation. Another mode of amplification is cooperation of PGs with cytokines at the transcription level. Typically, PGs and cytokines synergistically activate NF-?B to induce the expression of inflammation-related genes, one being COX-2 itself, which makes PG-mediated positive feedback loops. This signalling consequently enhances the expression of various NF-?B-induced genes including chemokines to macrophages and neutrophils, which enables sustained infiltration of these cells and further amplifies chronic inflammation. In addition, PGs are also involved in tissue remodelling such as fibrosis and angiogenesis. In this article, we review these findings and discuss their relevance to human diseases.

SUBMITTER: Yao C

PROVIDER: S-EPMC6329627 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Prostaglandin-cytokine crosstalk in chronic inflammation.

Yao Chengcan C Narumiya Shuh S

British journal of pharmacology 20181218 3

Chronic inflammation underlies various debilitating disorders including autoimmune, neurodegenerative, vascular and metabolic diseases as well as cancer, where aberrant activation of the innate and acquired immune systems is frequently seen. Since non-steroidal anti-inflammatory drugs exert their effects by inhibiting COX and suppressing PG biosynthesis, PGs have been traditionally thought to function mostly as mediators of acute inflammation. However, an inducible COX isoform, COX-2, is often h ...[more]

PMID: 30381825

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Prostaglandin-cytokine crosstalk in chronic inflammation.

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Prostaglandin-cytokine crosstalk in chronic inflammation.

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