Abstract
Bioactive lipid mediators play a major role in regulating inflammatory processes. Herein, early pro-inflammatory phases are characterized and regulated by prostanoids and leukotrienes, whereas specialized pro-resolving mediators (SPM), including lipoxins, resolvins, protectins, and maresins, dominate during the resolution phase. While pro-inflammatory properties of prostanoids have been studied extensively, their impact on later phases of the inflammatory process has been attributed mainly to their ability to initiate the lipid-mediator class switch towards SPM. Yet, there is accumulating evidence that prostanoids directly contribute to the resolution of inflammation and return to homeostasis. In this mini review, we summarize the current knowledge of the resolution-regulatory properties of prostanoids and discuss potential implications for anti-inflammatory, prostanoid-targeted therapeutic interventions.
Highlights
Inflammation is an integral part of protective host responses against pathogens or injury [1]
Since lipid mediators play a crucial, yet often ambivalent role during the inflammatory process, and prostanoid synthesis represents a major target for anti-inflammatory therapies, the present mini review aims to recapitulate the current understanding of the role of prostanoids in the context of resolution of inflammation
In contrast to the concept of a rapid return to homeostasis, recent reports provided evidence that resolution is followed by a longer lasting, immune-suppressive post-resolution phase characterized by infiltrating regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and MF, which might be decisive for a successful adaptation vs. chronic inflammation and/or autoimmunity [17,18,19]
Summary
Inflammation is an integral part of protective host responses against pathogens or injury [1]. To regain homeostasis resolution of inflammation represents an integral and crucial part of acute inflammation. While resolution was considered to merely represent the downregulation or inactivation of inflammatory mediators for a long time, it is appreciated to be active and complex, involving the formation of pro-resolving mediators [2]. Pro-resolving therapeutic approaches are increasingly being considered rather than anti-inflammatory ones as the latter might diminish the host response against pathogenic challenges [4, 5]. Since lipid mediators play a crucial, yet often ambivalent role during the inflammatory process, and prostanoid synthesis represents a major target for anti-inflammatory therapies, the present mini review aims to recapitulate the current understanding of the role of prostanoids in the context of resolution of inflammation
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