Resolvins suppress tumor growth and enhance cancer therapy

Sulciner, Megan L.; Serhan, Charles N.; Gilligan, Molly M.; Mudge, Dayna K.; Chang, Jaimie; Gartung, Allison; Lehner, Kristen; Bielenberg, Diane R.; Schmidt, Birgitta; Dalli, Jesmond; Greene, Emily; Gus-Brautbar, Yael; Piwowarski, Julia; Mammoto, Tadanori; Zurakowski, David; Perretti, Mauro; Sukhatme, Vikas P.; Kaipainen, Arja; Kieran, Mark W.; Huang, Sui; Panigrahy, Dipak

doi:10.1084/jem.20170681

Cited by 229 publications

(315 citation statements)

References 98 publications

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“…The phenotypic status of monocytes/macrophages are also essential in the pathogenesis of atherosclerosis and injury-induced neointimal hyperplasia (63,64). We and others have previously reported that RvE1 facilitates the resolution of inflammation by enhancing macrophage-mediated phagocytosis of apoptotic neutrophils (65), suppressing monocyte recruitment in ischemic hearts (24), and counterregulating the release of proinflammatory cytokines/chemokines by macrophages (66). These effects are mediated by the ChemR23 receptor (24).…”

Section: Discussionmentioning

confidence: 99%

Resolvin E1 attenuates inj ury‐induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration

et al. 2018

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Mechanical insults, such as stent implantation, can induce endothelial injury, vascular inflammation, and ultimately lead to vascular neointimal hyperplasia. Resolvin E1 (RvE1), derived from the ω3 fatty acid eicosapentaenoic acid, can facilitate the resolution of inflammation in many settings. We therefore aimed to determine if there was a role for RvE1 in preventing neointimal formation after arterial injury and to understand the underlying mechanisms. Vascular inflammation and neointimal hyperplasia were induced by wire injury in the femoral arteries of mice. Administration of exogenous RvE1 and endogenously generated RvE1 via dietary supplementation with eicosapentaenoic acid and aspirin markedly reduced vascular neointima formation in this model. Mechanistically, RvE1 was found to inhibit vascular neutrophil infiltration, promote macrophage polarization toward an M2-like phenotype, suppress T-cell trafficking by reducing RANTES secretion from vascular smooth muscle cells, and inhibit vascular smooth muscle cell migration. In summary, RvE1 demonstrated a protective role against vascular inflammation and remodeling in response to mechanical injury, suggesting that it may serve as an adjuvant therapeutic agent for percutaneous coronary interventions, such as stent implantation.-Liu, G., Gong, Y., Zhang, R., Piao, L., Li, X., Liu, Q., Yan, S., Shen, Y., Guo, S., Zhu, M., Yin, H., Funk, C. D., Zhang, J., Yu, Y. Resolvin E1 attenuates injury-induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration.

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Section: Discussionmentioning

confidence: 99%

Resolvin E1 attenuates inj ury‐induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration

et al. 2018

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“…These results show that various HFA products can be prepared from wild‐type and mutant enzymes at the preparative scale and isolated in good yields in enantiopure form. Because HFA derivatives of C 20 FAs are important lipid mediator molecules with anti‐inflammatory activity and therapeutic potential, further engineering of hydratases can contribute to green stereoselective routes for the enzymatic synthesis of desired hydroxy derivatives of EPA and AA for medical research. Moreover, all C 18 and C 20 HFAs produced by wild‐type and mutant enzymes can be tested for authentic biological activity alone or as components of FAHFAs, as well as for their physicomechanical properties for various bioplastic applications …”

Section: Discussionmentioning

confidence: 99%

Rational Engineering of Hydratase from Lactobacillus acidophilus Reveals Critical Residues Directing Substrate Specificity and Regioselectivity

et al. 2019

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Enzymatic conversion of fatty acids (FAs) by fatty acid hydratases (FAHs) presents a green and efficient route for high‐value hydroxy fatty acid (HFA) production. However, limited diversity was achieved among HFAs, to date, with respect to chain length and hydroxy position. In this study, two highly similar FAHs from Lactobacillus acidophilus were compared: FA‐HY2 has a narrow substrate scope and strict regioselectivity, whereas FA‐HY1 utilizes longer chain substrates and hydrates various double‐bond positions. It is revealed that three active‐site residues play a remarkable role in directing substrate specificity and regioselectivity of hydration. If these residues on FA‐HY2 are mutated to the corresponding ones in FA‐HY1, a significant expansion of substrate scope and a distinct enhancement in hydration of double bonds towards the ω‐end of FAs is observed. A three‐residue mutant of FA‐HY2 (TM‐FA‐HY2) displayed an impressive reversal of regioselectivity towards linoleic acid, shifting the ratio of the HFA regioisomers (10‐OH/13‐OH) from 99:1 to 12:88. Notable changes in regioselectivity were also observed for arachidonic acid and for C18 polyunsaturated fatty acid substrates. In addition, TM‐FA‐HY2 converted eicosapentaenoic acid into its 12‐hydroxy product with high conversion at the preparative scale. Furthermore, it is demonstrated that microalgae are a source of diverse FAs for HFA production. This study paves the way for tailor‐made FAH design to enable the production of diverse HFAs for various applications from the polymer industry to medical fields.

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“…Nonetheless, the exploration of potential secondary outcomes is beyond the scope of this paper, as it is the understanding of mechanisms that may be utilized by LCPUFAs‐ω3 to delay the progression to a pathological manifestation of obesity. This is important because it is known that resolvins (lipidic mediators derived from the LCPUFAs‐ω3 DHA) acutely turn off inflammation and stimulate a class of immune cells that limit or offset the cytokines effects on lipotoxicity . Based on this, the efficacy of adding DHA or resolvins to the existing therapies used to prevent disease progression is under investigation in other inflammatory diseases such as eczema, periodontal disease, and cancer.…”

Section: Discussionmentioning

confidence: 99%

A randomized control trial of the impact of LCPUFA‐ω3 supplementation on body weight and insulin resistance in pubertal children with obesity

et al. 2018

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Summary Background Paediatric obesity and insulin resistance (IR) are potentially reversible inflammatory conditions. Long chain polyunsaturated fatty acids omega‐3 (LCPUFA‐ω3) show anti‐inflammatory and metabolic properties, but their clinical efficacy is unclear. Objective The objective of this study is to evaluate whether supplementation with LCPUFA‐ω3 for 3 months reduces insulin resistance and weight to adolescents with obesity. Methods Double‐blind trial of 366 adolescents with obesity randomly assigned to 1.2‐g LCPUFA‐ω3 (DO3) or 1‐g sunflower oil (DP) daily for 3 months; both groups received an energy‐restricted diet. Children attended monthly for anthropometric, dietary, and clinical measurements. Basal and final blood samples were obtained to measure metabolic markers and erythrocytes fatty acids. Regression models were used for analysis. Results A total of 119 DO3 and 126 DP children completed follow‐up. At baseline, 92% of children presented IR, 66% hypertriglyceridemia, 37% low‐grade inflammation, and 32% metabolic syndrome. Despite erythrocytes LCPUFA‐ω3 increased more in DO3 (Median differences = 0.984 w/w%; 95 IC = 0.47, 1.53, P < 0.001), body weight, insulin, and HOMA changed similarly in both groups at the end of intervention. Adjusting for basal values, changes in weight, insulin, and HOMA was not related with supplementation. Conclusions Supplementation with LCPUFA‐ω3 does not affect body weight or insulin in adolescents with obesity.

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Resolvins suppress tumor growth and enhance cancer therapy

Cited by 229 publications

References 98 publications

Resolvin E1 attenuates inj ury‐induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration

Resolvin E1 attenuates inj ury‐induced vascular neointimal formation by inhibition of inflammatory responses and vascular smooth muscle cell migration

Rational Engineering of Hydratase from Lactobacillus acidophilus Reveals Critical Residues Directing Substrate Specificity and Regioselectivity

A randomized control trial of the impact of LCPUFA‐ω3 supplementation on body weight and insulin resistance in pubertal children with obesity

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