Exhaustive acute exercise-induced ER stress is attenuated in IL-6-knockout mice

Abstract

The endoplasmic reticulum (ER) stress and inflammation relationship occurs at different levels and is essential for the adequate homeostatic function of cellular systems, becoming harmful when chronically engaged. Intense physical exercise enhances serum levels of interleukin 6 (IL-6). In response to a chronic exhaustive physical exercise protocol, our research group verified an increase of the IL-6 concentration and ER stress proteins in extensor digitorium longus (EDL) and soleus. Based on these results, we hypothesized that IL-6-knockout mice would demonstrate a lower modulation in the ER stress proteins compared to the wild-type mice. To clarify the relationship between exercise-induced IL-6 increased and ER stress, we studied the effects of an acute exhaustive physical exercise protocol on the levels of ER stress proteins in the skeletal muscles of IL-6-knockout (KO) mice. The WT group displayed a higher exhaustion time compared to the IL-6 KO group. After 1 h of the acute exercise protocol, the serum levels of IL-6 and IL-10 were enhanced in the WT group. Independent of the experimental group, the CHOP and cleaved caspase 12/total caspase 12 ratio in EDL as well as ATF6 and CHOP in soleus were sensitive to the acute exercise protocol. Compared to the WT group, the oscillation patterns over time of BiP in EDL and soleus as well as of peIF2-alpha/eIF2-alpha ratio in soleus were attenuated for the IL-6 KO group. In conclusion, IL-6 seems to be related with the ER stress homeostasis, once knockout mice presented attenuation of BiP in EDL and soleus as well as of pEiF2-alpha/EiF2-alpha ratio in soleus after the acute exhaustive physical exercise protocol.

Evaluation of the Efficacy of Supplementation with Planox® Lemon Verbena Extract in Improving Oxidative Stress and Muscle Damage: A Double-Blind Controlled Trial

“…This study explored the effects of a lemon verbena extract supplement containing 9% acteoside and isoacteoside in reducing muscle damage and promoting muscle strength recovery. Based on the results, we found that although the supplementation of lemon verbena extract produced no significant difference in strength performance, it effectively reduced muscle damage indicators and indicating possible pro-inflammatory stress caused by exercise, such as CK and IL-6 33 . In addition, subjects' subjective feelings and objective detection of pain were also significantly improved.…”

Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways

“…Kim et al emphasized the link between ERS in the skeletal muscle and exercise and suggested that ERS was activated in the human skeletal muscle after exercise [121]. Myokines, such as fibroblast growth factor 21 and interleukin-6 (IL-6), were upregulated by enhanced ERS in the skeletal muscle during a short-term exercise [122,123]. Circulating myokines enhanced β-oxidation and repressed lipogenesis in the liver, increased glucose and lipid uptake in adipocytes, and promoted hepatic glycolysis and lipolysis to fuel the muscle [124,125].…”

“…ERS induced by palmitate could increase the expression of HPS in hepatocytes and further contribute to the IR in the skeletal muscle via the epidermal growth factor receptor (EGFR)/JNK-mediated pathway [ 135 ]. In turn, ERS induced by exercise in the skeletal muscle could increase the release of myokines such as FGF21 and IL-6 and further reduce hepatic IR in NAFLD ultimately [ 122 , 123 ].…”

Carboxylesterases: Pharmacological Inhibition Regulated Expression and Transcriptional Involvement of Nuclear Receptors and other Transcription Factors

“…Interlekin-6 (IL-6) and lipopolysaccharides (LPS). IL-6 is generally considered as a proinflammatory cytokine, although it has anti-inflammatory effect [106][107][108]. Nevertheless, this cytokine has been shown to downregulate the expression of both CES1 and CES2 [109].…”