The resolution of inflammation: New mechanisms in patho-physiology open opportunities for pharmacology

Perretti, Mauro

doi:10.1016/j.smim.2015.06.001

Cited by 28 publications

(28 citation statements)

References 10 publications

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“…However, it has recently become evident that active resolution of inflammation involves the biosynthesis of pro-resolving mediators that, as a genus, are just as diverse as the initiators of inflammation 24–33 . Thus, critical to determining the fate of an inflammatory response is the balance of pro-inflammatory and pro-resolving mediators that are produced in the exudate in a temporal manner.…”

Section: Acute Inflammation and Its Resolutionmentioning

confidence: 99%

“…In addition to lipid mediators of resolution, other important mediators of the resolution program have emerged and include proteins and bioactive peptides (e.g., annexin A1, galectin 1, melanocortins) and gases (nitric oxide, hydrogen sulfide, carbon monoxide). Readers are referred to recent reviews covering each of these mediators in detail 24–33 . Here, we focus primarily on the biosynthesis and biological actions of resolvins in the inflammation-resolution program.…”

Section: Pro-resolving Mediatorsmentioning

confidence: 99%

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Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Sansbury

Spite

2016

Circulation Research

172

103

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Acute inflammation is a host-protective response that is mounted in response to tissue injury and infection. Initiated and perpetuated by exogenous and endogenous mediators, acute inflammation must be resolved for tissue repair to proceed and for homeostasis to be restored. Resolution of inflammation is an actively regulated process governed by an array of mediators as diverse as those that initiate inflammation. Among these, resolvins have emerged as a genus of evolutionarily conserved pro-resolving mediators that act on specific cellular receptors to regulate leukocyte trafficking and blunt production of inflammatory mediators, while promoting clearance of dead cells and tissue repair. Given that chronic unresolved inflammation is emerging as a central causative factor in the development of cardiovascular diseases, an understanding of the endogenous processes that govern normal resolution of acute inflammation is critical for determining why sterile maladaptive cardiovascular inflammation perpetuates. Here, we provide an overview of the process of resolution with a focus on the enzymatic biosynthesis and receptor-dependent actions of resolvins and related pro-resolving mediators in immunity, thrombosis and vascular biology. We discuss how nutritional and current therapeutic approaches modulate resolution and propose that harnessing resolution concepts could potentially lead to the development of new approaches for treating chronic cardiovascular inflammation in a manner that is not host-disruptive.

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Section: Acute Inflammation and Its Resolutionmentioning

confidence: 99%

Section: Pro-resolving Mediatorsmentioning

confidence: 99%

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Sansbury

Spite

2016

Circulation Research

172

103

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“…The identification of pro-resolving pathways and mediators that expedite resolution of inflammation was rapidly embraced by colleagues studying immunopharmacology and opened the potential for considering new therapeutic directions (Gilroy et al, 2004; Serhan et al, 2007). The cells, mediators, and mechanisms in the resolution of inflammation are the subjects of several recent in-depth reviews that interested readers are directed to (Jones et al, 2016; Perretti, 2015; Robb et al, 2016; Tabas and Glass, 2013; Fullerton and Gilroy, 2016; Buckley et al, 2014; Spite et al, 2013; Serhan et al, 2015b; Serhan et al, 2015a). …”

Section: Introductionmentioning

confidence: 99%

Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors

Chiang

Serhan

2017

Molecular Aspects of Medicine

284

232

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The acute inflammatory response is host protective to contain foreign invaders. Many of today’s pharmacopeia that block pro-inflammatory chemical mediators can cause serious unwanted side effects such as immune suppression. Uncontrolled inflammation is now considered a pathophysiologic basis associated with, many widely occurring diseases such as cardiovascular disease, neurodegenerative diseases, diabetes, obesity and asthma, as well as the classic inflammatory diseases, e.g. arthritis, periodontal diseases. The inflammatory response is designated to be a self-limited process that produces a superfamily of chemical mediators that stimulate resolution of inflammatory responses. Specialized proresolving mediators (SPM) uncovered in recent years are endogenous mediators that include omega-3-derived families resolvins, protectins and maresins, as well as arachidonic acid-derived (n-6) lipoxins that stimulate and promote resolution of inflammation, clearance of microbes, reduce pain and promote tissue regeneration via novel mechanisms. Here, we review recent evidence from human and preclinical animal studies, together with the structural and functional elucidation of SPM indicating the SPM as physiologic mediators and pharmacologic agonists that stimulate resolution of inflammation and infection. These results suggest that it is time to develop immunoresolvents as agonists for testing resolution pharmacology in nutrition and health as well as in human diseases and during surgery.

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“…These early events initiate the recruitment of neutrophils to the injured tissue. These cells produce reactive oxygen species, release antibacterial proteins, and ingest microorganisms and dead cells [1,2,3,4]. Neutrophil extracellular traps, which are composed of DNA, chromatin, antibacterial proteins and enzymes, immobilize and eventually kill pathogens.…”

Section: Introductionmentioning

confidence: 99%

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

Buechler

Pohl

Aslanidis

2017

IJMS

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Inflammation is a complex response of the body to exogenous and endogenous insults. Chronic and systemic diseases are attributed to uncontrolled inflammation. Molecules involved in the initiation of inflammation are very well studied while pathways regulating its resolution are insufficiently investigated. Approaches to down-modulate mediators relevant for the onset and duration of inflammation are successful in some chronic diseases, while all of them have failed in sepsis patients. Inflammation and immune suppression characterize sepsis, indicating that anti-inflammatory strategies alone are inappropriate for its therapy. Heme oxygenase 1 is a sensitive marker for oxidative stress and is upregulated in inflammation. Carbon monoxide, which is produced by this enzyme, initiates multiple anti-inflammatory and pro-resolving activities with higher production of omega-3 fatty acid-derived lipid metabolites being one of its protective actions. Pro-resolving lipids named maresins, resolvins and protectins originate from the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid while lipoxins are derived from arachidonic acid. These endogenously produced lipids do not simply limit inflammation but actively contribute to its resolution, and thus provide an opportunity to combat chronic inflammatory diseases and eventually sepsis.

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The resolution of inflammation: New mechanisms in patho-physiology open opportunities for pharmacology

Cited by 28 publications

References 10 publications

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Resolution of Acute Inflammation and the Role of Resolvins in Immunity, Thrombosis, and Vascular Biology

Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors

Pro-Resolving Molecules—New Approaches to Treat Sepsis?

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