The Impact of CB1 Receptor on Inflammation in Skeletal Muscle Cells

Abstract

Background Various factors trigger the inflammatory response and cytokine activation in skeletal muscle. Inflamed muscle will exhibit significant levels of inflammation and cytokine activity. Interleukin-6 (IL-6), a pro-inflammatory cytokine, exerts pleiotropic effects on skeletal muscle. Endocannabinoid produced by all cell types binds to a class of G protein-coupled receptors, in particular cannabinoid CB1 receptors, to induce skeletal muscle actions. Objective The purpose of this research was to discover whether activation of cannabinoid CB1 receptors in L6 skeletal muscle cells may promote IL-6 gene expression. Materials and Methods L6 skeletal muscle cells were cultured in 25 cm 2 flasks and quantitative reverse transcription-polymerase chain reaction (probe-based) utilised to quantify IL-6 gene expression levels among different treatment settings. Results Arachidonyl-2ʹ-chloroethylamide (ACEA) 10 nM, a persistent selective CB1 receptor agonist, promotes IL-6 gene expression in a time-dependent manner. Rimonabant 100 nM, a selective cannabinoid CB1 receptor antagonist, blocks the impact of ACEA. However, insulin does not change IL-6 gene expression. Conclusion For the first time, a unique link between ACEA and IL-6 up-regulation has been established; IL-6 up-regulation generated by ACEA is mediated in skeletal muscle through cannabinoid CB1 receptor activation. As a result, cannabinoid CB1 receptors may be useful pharmaceutical targets in the treatment of inflammation and related disorders in skeletal muscle tissues.

The Impact of CB1 Receptor on Nuclear Receptors in Skeletal Muscle Cells

“…Passaging of the cells occurred at around 60–70% confluency, while changing of the medium was carried out thrice weekly, as shown in Figure 1 . The confluent cells underwent 14 days of further culturing in 25 cm 2 flasks in order to allow myotubes to form, in alignment with the protocols outlined in my previous publications [ 15 , 16 , 17 ], albeit with minor modifications ( Figure 1 ). After around two weeks of culturing, the 70–90% confluent myotubes were then exposed to 2% ( v / v ) delipidated serum for a period of 5 h before undergoing starvation for a further 19 h. Figure 1 then shows that the cells were treated for varying periods of time (1, 3, 5, and 24 h) with vehicle (0.1% DMSO), rimonabant 100 nM, ACEA 10 nM, and insulin 100 nM.…”

“…One of the largest tissues of human body is the skeletal muscle. In the case of rats, it constitutes majority of the body weight [ 14 , 15 , 16 , 17 ]. In general, it has been recognized as the main site of metabolism of fatty acids and glucose [ 18 , 19 , 20 , 21 , 22 , 23 ].…”

“…As this tissue is capable of oxidizing fatty acid and glucose, its role in metabolic disorders is also important [ 25 ]. A number of scientists sometimes refer skeletal muscle as an endocrine organ considering discharge of inflammatory mediators by this tissue [ 17 ]. Taken together, skeletal muscle is essentially involved in glycemic control, sustaining glucose homeostasis and in regulating metabolic reactions of human system [ 24 ].…”

(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders

“…CB1 receptors play pleiotropic homeostatic functions, such as neuromodulation in the brain, often resulting in appetite and energy intake stimulation [ 7 , 8 ]. In addition, lately, the pharmaceutical importance of targeting the CB1 receptors has also been demonstrated in skeletal muscle cells [ 9 – 11 ]. Some of the observed effects were suggested to be regulated via downregulation of the pro-inflammatory cascades, particularly ablating the cytokine activity of interleukin-6 (IL-6) [ 9 ] and orphan nuclear receptor NR4A family – NR4A1, NR4A2, and NR4A3 [ 10 ].…”

“…In addition, lately, the pharmaceutical importance of targeting the CB1 receptors has also been demonstrated in skeletal muscle cells [ 9 – 11 ]. Some of the observed effects were suggested to be regulated via downregulation of the pro-inflammatory cascades, particularly ablating the cytokine activity of interleukin-6 (IL-6) [ 9 ] and orphan nuclear receptor NR4A family – NR4A1, NR4A2, and NR4A3 [ 10 ]. On the contrary, CB2 receptors preferentially hold immunomodulatory functions, often resulting in the inhibition of inflammation [ 12 ].…”