Increased Circulating Levels of Interleukin-6 Affect the Redox Balance in Skeletal Muscle.
Laura ForcinaCarmen MianoBianca Maria ScicchitanoEmanuele RizzutoMaria Grazia BerardinelliFabrizio De BenedettiLaura PelosiAntonio MusaròPublished in: Oxidative medicine and cellular longevity (2019)
The extent of oxidative stress and chronic inflammation are closely related events which coexist in a muscle environment under pathologic conditions. It has been generally accepted that the inflammatory cells, as well as myofibers, are sources of reactive species which are, in turn, able to amplify the activation of proinflammatory pathways. However, the precise mechanism underlining the physiopathologic interplay between ROS generation and inflammatory response has to be fully clarified. Thus, the identification of key molecular players in the interconnected pathogenic network between the two processes might help to design more specific therapeutic approaches for degenerative diseases. Here, we investigated whether elevated circulating levels of the proinflammatory cytokine Interleukin-6 (IL-6) are sufficient to perturb the physiologic redox balance in skeletal muscle, independently of tissue damage and inflammatory response. We observed that the overexpression of circulating IL-6 enhances the generation and accumulation of free radicals in the diaphragm muscle of adult NSE/IL-6 mice, by deregulating redox-associated molecular circuits and impinging the nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated antioxidant response. Our findings are coherent with a model in which uncontrolled levels of IL-6 in the bloodstream can influence the local redox homeostasis, inducing the establishment of prooxidative conditions in skeletal muscle tissue.
Keyphrases
- skeletal muscle
- oxidative stress
- inflammatory response
- induced apoptosis
- insulin resistance
- nuclear factor
- dna damage
- toll like receptor
- lipopolysaccharide induced
- diabetic rats
- ischemia reperfusion injury
- cell death
- neoadjuvant chemotherapy
- type diabetes
- adipose tissue
- squamous cell carcinoma
- cell proliferation
- electron transfer
- endoplasmic reticulum stress
- signaling pathway
- intensive care unit
- escherichia coli
- drinking water
- high fat diet induced
- multidrug resistant
- young adults
- transcription factor
- extracorporeal membrane oxygenation
- radiation therapy
- mechanical ventilation
- cell cycle arrest
- childhood cancer
- genetic diversity
- gram negative