Anti-inflammatory properties of prostaglandin E2: Deletion of microsomal prostaglandin E synthase-1 exacerbates non-immune inflammatory arthritis in mice

Frolov, Andrey; Yang, Lihua; Dong, Hua; Hammock, Bruce D.; Crofford, Leslie J.

doi:10.1016/j.plefa.2013.08.003

Cited by 44 publications

(34 citation statements)

References 45 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with this interpretation, rapid appearance of lipid droplets in ATMs during a fast has been described ( 8 ). In addition, PGE 2 can suppress production of acute infl ammatory mediators and inhibit attraction of proinfl ammatory cells ( 31 ). Suppressing PGE 2 production by deletion of microsomal prostaglandin E synthase-1 exacerbates neutrophilmediated infl ammation ( 11 ) while activation of the PGE 2 receptor EP4 inhibits infl ammasome activation through EP4 receptor and intracellular cAMP in human macrophages ( 32 ).…”

Section: Discussionmentioning

confidence: 88%

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

Cifarelli

Sun

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

Supplementary key words adipose tissue • cyclooxygenase • eicosanoids • extracellular signal-regulated kinase • fatty acid • infl ammation • lipaseAdipose tissue is the major repository of excess energy stored in the form of triacylglycerol (TAG). During energy need, adipocyte lipolysis involving the hydrolysis of TAG releases FFAs for energy production by different tissues ( 1, 2 ). Adipose tissue also secretes various adipokines, which infl uence energy homeostasis and insulin sensitivity of distant tissues ( 3, 4 ). In addition to its important role in metabolic regulation, adipose tissue modulates the immune system by recruiting and activating lymphoid and myeloid cells when adipocyte fat storage is exaggerated as occurs in obesity ( 5 ). In obese individuals, there is a strong positive correlation between adipocyte size and the accumulation of proinfl ammatory adipose tissue macrophages (ATMs) ( 6, 7 ).However, ATM recruitment also occurs in mice after fasting or with calorie restriction ( 8 ) and in obese patients maintained on low-calorie diets during early weight loss ( 9 ), but under these conditions, it does not associate with infl ammation. The above fi ndings suggest that the mechanisms that operate in ATM recruitment in obesity or calorie restriction are not identical. Both fasting and pharmaceutically induced lipolysis increase macrophage content in adipose tissue, and lipolysis measures correlate with increased ATM content independent of adiposity ( 10 ). This suggests that lipid turnover and not lipid accumulation per se is Abstract Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic infl ammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinfl ammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specifi c lipid mediators with anti-infl ammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E 2 (PGE 2 ) and prostaglandin D 2 (PGD 2 ), refl ecting cytosolic phospholipase A 2 ␣ activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-infl ammatory PGE 2 potently induced macrophage migration while different FFAs and PGD 2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE 2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE 2 with infl ammation suppressive properties plays a signifi cant rol...

show abstract

Section: Discussionmentioning

confidence: 88%

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

Cifarelli

Sun

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…This ambivalent role of mPGES-1 in cancer might be related to the dual character of PGE 2 as non-resolving/pro-tumoral and pro-resolving/antitumoral mediator. In fact, the link between cancer and chronic inflammation becomes increasingly evident [15], and the importance of mPGES-1 for the resolution of inflammation has been demonstrated in animal models of neuroinflammation [17] and non-autoimmune arthritis [18].…”

Section: Page 9 Of 59mentioning

confidence: 99%

“…The role of mPGES-1 in regulating lipid mediator levels others than prostanoids was addressed by only few studies, which, however, suggest comprehensive changes of the nonprostanoid lipid mediator profile [18,106]. The mechanisms underlying these changes are not fully understood but most likely also include indirect effects of mPGES-1-derived PGE 2 on immune cell recruitment, activation and differentiation.…”

Section: Page 29 Of 59mentioning

confidence: 99%

“…observed a more severe disease progression for collagen antibody-induced arthritis in mPGES-1-deficient mice, which was not only associated with a massive suppression of PGE 2 formation but also with lower production of other COX-, 5-, 12-, 15-LO-and cytochrome P 450 monooxygenase-derived lipid mediators including pro-resolving PGD 2 and epoxyeicosatetraenoic acids (EETs)[18]. Idborg et al investigated the effect of mPGES-1 deletion on a of eicosanoids produced by LPS-activated murine peritoneal macrophages and…”

mentioning

confidence: 99%

See 1 more Smart Citation

Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders

Koeberle

Werz

2015

Biochemical Pharmacology

112

View full text Add to dashboard Cite

“…Although these mediators intervene in both the establishment and resolution of the inflammatory response, their net effect is predominantly proinflammatory. [19,20] In contrast, ALA (n-3) is a precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), from which 3-series PGs and TXs, as well as 5-series LTs, lipoxins, resolvins and neuroprotectins are derived. These compounds have chiefly anti-inflammatory effects, [17] which is why current nutritional guidelines are oriented towards an increase in n-3 PUFAs intake.…”

Section: [18]mentioning

confidence: 99%

Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function

Calvo¹,

Martínez²,

Torres³

et al. 2017

View full text Add to dashboard Cite

How to cite this article: Calvo MJ, Martínez MS, Torres W, Chávez-Castillo M, Luzardo E, Villasmil N, Salazar J, Velasco M, Bermúdez V. Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function. Vessel Plus 2017;1:116-28.Given the notorious impact of cardiovascular disease (CVD) as the current leading cause of mortality worldwide, the prevention, identification and management of CV risk factors represents a priority in daily clinical practice. Several studies have shown the beneficial effects of dietary omega-3 polyunsaturated fatty acids (PUFAs) on CV health. Their derivatives, eicosapentaenoic acid and docosahexaenoic acid, intervene in multiple metabolic pathways, including: regulation of the inflammatory response, by reducing the synthesis of pro-inflammatory cytokines; regulation of platelet aggregation, activation and adhesion, by modulating thromboxane A2 and plasminogen activator inhibitor-1 activity; regulation of the coagulation pathways, by reducing the carboxylation of vitamin K-dependent coagulation factors; improvement of endothelial function, given their effects on prostaglandin synthesis and endothelial nitric oxide synthase; reduction of serum lipids, through their effects on the hepatic synthesis of triacylglycerides, beta-oxidation of fatty acids and lipoprotein catabolism; and improvement of myocardial function via their membrane-stabilizing effects, and an increase in fluidity, size and distribution of membrane lipid rafts. Nevertheless, these effects appear to vary according to the type of PUFA ingested, dietary sources, daily dosing and individual factors inherent to the subject. Therefore, further studies are required to determine the ideal supplementation for each kind of patient and their particular CV profiles. Key words:Cardiovascular disease, omega-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaeonic acid ABSTRACTArticle history:

show abstract

Anti-inflammatory properties of prostaglandin E2: Deletion of microsomal prostaglandin E synthase-1 exacerbates non-immune inflammatory arthritis in mice

Cited by 44 publications

References 45 publications

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment

Perspective of microsomal prostaglandin E2 synthase-1 as drug target in inflammation-related disorders

Omega-3 polyunsaturated fatty acids and cardiovascular health: a molecular view into structure and function

Contact Info

Product

Resources

About