Old and new generation lipid mediators in acute inflammation and resolution

Stables, Melanie; Gilroy, Derek W.

doi:10.1016/j.plipres.2010.07.005

Cited by 278 publications

(235 citation statements)

References 315 publications

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Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

“…9 Indeed, fracture calluses of COX-2-null mice have significantly higher levels of LTB 4 . Addition of LTB 4 or especially 5-hydroxyeicosatetraenoic acid to cultured calvarial cells impairs bone formation in vitro. 25,26 Further, bone cortical thickness is increased in mice lacking 5-LO, again suggesting that 5-LO lipid Figure 2 Histomorphometric analysis of fracture healing in COX-deficient mice (Ptgs1 tm1Unc and Ptgs2 tm1Unc ).…”

Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

“…LTC 4 is subsequently modified to create leukotriene D 4 and leukotriene E 4 . The effects of inhibiting these enzyme activities on fracture healing have not been reported.…”

Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

“…The effects of inhibiting these enzyme activities on fracture healing have not been reported. However, LTA 4 hydrolase and LTC 4 synthase are expressed in chondrocytes and can mediate transcellular synthesis of LTB 4 and LTC 4 . 7 Interestingly, LTA 4 hydrolase shares many structural properties with angiotensin-converting enzyme (ACE) such that some ACE inhibitors can also inhibit LTA 4 hydrolase and certain ACE inhibitors have been shown to promote fracture healing.…”

Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

“…3 Those lipid mediators derived from O-6 fatty acids that include arachidonic acid (AA; 20:4n-6) and O-3 fatty acids that include eicosapentaenoic acid (EPA; 22:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) are known to be potent regulators of inflammation. 4 In general, O-6-derived lipid mediators promote inflammation, whereas O-3-derived lipid mediators resolve inflammation. As described below, manipulation of these pathways can profoundly impair or promote bone regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Fracture healing and lipid mediators

O’Connor¹,

Manigrasso²,

Kim³

et al. 2014

BoneKEy Reports

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Lipid mediators regulate bone regeneration during fracture healing. Prostaglandins and leukotrienes are well-known lipid mediators that regulate inflammation and are synthesized from the O-6 fatty acid, arachidonic acid. Cyclooxygenase (COX-1 or COX-2) and 5-lipoxygenase (5-LO) catalyze the initial enzymatic steps in the synthesis of prostaglandins and leukotrienes, respectively. Inhibition or genetic ablation of COX-2 activity impairs fracture healing in animal models. Genetic ablation of COX-1 does not affect the fracture callus strength in mice, suggesting that COX-2 activity is primarily responsible for regulating fracture healing. Inhibition of cyclooxygenase activity with nonsteroidal anti-inflammatory drugs (NSAIDs) is performed clinically to reduce heterotopic ossification, although clinical evidence that NSAID treatment impairs fracture healing remains controversial. In contrast, inhibition or genetic ablation of 5-LO activity accelerates fracture healing in animal models. Even though prostaglandins and leukotrienes regulate inflammation, loss of COX-2 or 5-LO activity appears to primarily affect chondrogenesis during fracture healing. Prostaglandin or prostaglandin analog treatment, prostaglandin-specific synthase inhibition and prostaglandin or leukotriene receptor antagonism also affect callus chondrogenesis. Unlike the O-6-derived lipid mediators, lipid mediators derived from O-3 fatty acids, such as resolvin E 1 (RvE1), have anti-inflammatory activity. In vivo, RvE1 can inhibit osteoclastogenesis and limit bone resorption. Although O-6 and O-3 lipid mediators have clear-cut effects on inflammation, the role of these lipid mediators in bone regeneration is more complex, with apparent effects on callus chondrogenesis and bone remodeling.

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Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

“…LTC 4 is subsequently modified to create leukotriene D 4 and leukotriene E 4 . The effects of inhibiting these enzyme activities on fracture healing have not been reported.…”

Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

Section: -Lipoxygenase (5-lo)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fracture healing and lipid mediators

O’Connor¹,

Manigrasso²,

Kim³

et al. 2014

BoneKEy Reports

View full text Add to dashboard Cite

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From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

2017

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The emerging diverse roles of ether (phospho)lipids in nervous system development and function in health and disease are currently attracting growing interest. Plasmalogens, a subgroup of ether lipids, are important membrane components involved in vesicle fusion and membrane raft composition. They store polyunsaturated fatty acids and may serve as antioxidants. Ether lipid metabolites act as precursors for the formation of glycosyl-phosphatidyl-inositol anchors; others, like platelet-activating factor, are implicated in signaling functions. Consolidating the available information, we attempt to provide molecular explanations for the dramatic neurological phenotype in ether lipid-deficient human patients and mice by linking individual functional properties of ether lipids with pathological features. Furthermore, recent publications have identified altered ether lipid levels in the context of many acquired neurological disorders including Alzheimer's disease (AD) and autism. Finally, current efforts to restore ether lipids in peroxisomal disorders as well as AD are critically reviewed.

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Roles of resolvins in the resolution of acute inflammation

Xuan

Fan

2014

Cell Biology International

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Resolution is an active process that terminates inflammatory response to maintain health. Acute inflammation and its timely resolution are important in host response to danger signals. Unresolved inflammation is associated with widely recurrent diseases. Resolvins, including the D and E series, are endogenous lipid mediators generated during the resolution phase of acute of inflammation from the ω-3 PUFAs, DHA, and EPA. They have anti-inflammatory and pro-resolving properties that have been determined in many inflammation studies in animal models. In this review, we provide an updated overview of biosynthesis, actions, and signaling pathways of resolvins, thereby underscoring their diverse protective roles and introducing novel therapeutic strategies for inflammation-associated diseases.

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Old and new generation lipid mediators in acute inflammation and resolution

Cited by 278 publications

References 315 publications

Fracture healing and lipid mediators

Fracture healing and lipid mediators

From peroxisomal disorders to common neurodegenerative diseases – the role of ether phospholipids in the nervous system

Roles of resolvins in the resolution of acute inflammation

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