Resolvin E1 (R_vE₁) attenuates LPS induced inflammation and subsequent atrophy in C2C12 myotubes

Abstract

Resolution of inflammation is now known to be an active process which in part is instigated and controlled by specialized pro-resolving lipid mediators (SPM's) derived from dietary omega-3 fatty acids. Resolvin E1 (R E ) is one of these SPM's derived from the omega-3 fatty acid eicosapentaenoic acid. Using both molecular and phenotypic functional measures we report that in a model of Lipopolysaccharide (LPS) induced inflammation, R E attenuated mRNA levels of both interlukin-6 and monocyte chemoattractant protein-1 whilst having no effect on tumor necrosis factor-α or interlukin-1β in C2C12 skeletal muscle myotubes. Findings at the molecular level were transferred into similar changes in extracellular protein levels of the corresponding genes with the greatest attenuation being noted in IL-6 protein concentrations. R E instigated beneficial morphological changes through the prevention of LPS induced skeletal muscle atrophy, in tandem with attenuation of the LPS induced reduction in contractile force in tissue engineered skeletal muscle. These findings demonstrate, in our model of endotoxin induced inflammation in skeletal muscle, that R E has pro-resolving properties in this cell type. Our data provides rationale for further investigation into the mechanistic action of R E in skeletal muscle, with the vision of having potential benefits for the prevention/resolution of in-vivo skeletal muscle atrophy.

RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome

“…In the current study, serum cytokine levels were elevated in Ts65Dn mice and we further demonstrated that RvE1 administration restored normal levels of several cytokines involved in innate immunity (IL‐1ɑ, IL‐1β, IL‐6, and TNF‐ɑ). These results further indicate the potency of RvE1 in reducing inflammation in different tissues and corroborate previous findings in other mouse models of AD (Baker et al, ; Kantarci et al, ). Furthermore, modulating inflammation by chronically upregulating pro‐resolving mechanisms should be considered as a novel alternative to anti‐inflammatory approaches, such as chronic minocycline treatment (Hunter, Bachman, & Granholm, ; Hunter, Quintero, et al, ).…”

Immunoresolvents Support Skeletal Myofiber Regeneration via Actions on Myeloid and Muscle Stem Cells

“…RvD1 also directly reduced LPS stimulated mRNA expression of IL-6 and TNFα, as well as secretion of MCP-1 protein by C2C12 myotubes cultured in-vitro. Consistent with these observations, n-3 EPA derived resolvin E1 (RvE1) directly inhibits cytokine production by muscle cells (88).…”

Crosstalk Between the Gut Microbiome and Bioactive Lipids: Therapeutic Targets in Cognitive Frailty

“…Nonetheless, the current state of the art points to promising effects using different members of the SPM group and the eCB system on several chronic diseases. Therefore, the modulation of several SPM members and the eCB system may lead to potential routes for therapeutic development through the selective activation of anti-inflammatory bioactive lipids (lipoxins, resolvins, protectins, maresins, PEA, OEA) (64,(89)(90)(91)117) or the inhibition/antagonism of their receptors and enzymes (Figure 4).…”

“…This process protected rodent brains from neuroinflammation, synaptic dysfunction, and cognitive decline (89). In an in vivo model of LPS-induced inflammation, the activation of resolvin E1 attenuated mRNA levels of several pro-inflammatory cytokines and chemokines (IL-6 and monocyte chemoattractant protein-1) in C2C12 skeletal muscle myotubes, preventing skeletal muscle atrophy in this cell type (90). In an adult male Sprague-Dawley rat model, lipoxin A4-a known SPM with powerful anti-inflammatory functions-exerted beneficial effects in cognitive impairment induced by chronic cerebral hypoperfusion (91).…”

“…Several studies also support the use of SPMs as a modulation strategy to counterbalance skeletal muscle atrophy. For instance, in an in vitro study, the use of resolvin E1 attenuated the mRNA levels of several pro-inflammatory cytokines and chemokines in C2C12 skeletal muscle myotubes, preventing LPS-induced skeletal muscle atrophy (90). Moreover, supplementation in rodents with fish oil (rich in ω-3 PUFA) alleviated skeletal muscle atrophy during immobilization through attenuating disturbances in the activation of the Akt and p70-S6 protein kinases, muscle atrophy F-box, and muscle RING finger 1 gene expression, with partial preservation of myosin heavy chain content (102).…”