In yet another discovery pointing to the benefits of physical activity, human muscle has been shown to stave off the destructive effects of chronic inflammation through exercise.
“Lots of processes are taking place throughout the human body during exercise, and it is difficult to tease apart which systems and cells are doing what inside an active person,” said Nenad Bursac, professor of biomedical engineering at Duke. “Our engineered muscle platform is modular, meaning we can mix and match various types of cells and tissue components if we want to. But in this case, we discovered that the muscle cells were capable of taking anti-inflammatory actions all on their own.”
Inflammation can be beneficial, such as a low-level response which clears out debris and helps regeneration, or it can be detrimental, such as the lethal COVID cytokine storms. Chronic inflammation as in arthritis or sarcopenia can be damaging as it takes away the ability of muscle to contract, resulting in weakening.
One inflammatory molecule in particular, interferon gamma, has been shown to be associated in many different types of muscular wasting. Interferon gamma is primarily produced by T lymphocytes and natural killer (NK) cells.
“We know that chronic inflammatory diseases induce muscle atrophy, but we wanted to see if the same thing would happen to our engineered human muscles grown in a Petri dish,” said Zhaowei Chen, a postdoctoral researcher in Bursac’s laboratory and first author of the paper. “Not only did we confirm that interferon gamma primarily works through a specific signaling pathway, we showed that exercising muscle cells can directly counter this pro-inflammatory signaling independent of the presence of other cell types or tissues.”
To determine if interferon gamma was the true culprit, Berac and Chen grew contractile human muscle tissue in vitro, then flooded it with interferon gamma over seven days. As predicted, the muscle shrank and lost strength,
They then applied interferon gamma again, but this time electrically stimulating the muscle to contract. They expected the simulated exercise to result in some muscle regrowth as seen in their previous studies, but to their surprise, the muscle suffered almost no effect from the chronic inflammation.They demonstrated that exercise blocked a particular molecular pathway as used in a pair of drugs to treat rheumatoid arthritis, tofacitinib and baricitinib, which produce the same anti-inflammatory effect.
“When exercising, the muscle cells themselves were directly opposing the pro-inflammatory signal induced by interferon gamma, which we did not expect to happen,” Bursac said. “These results show just how valuable lab-grown human muscles might be in discovering new mechanisms of disease and potential treatments. There are notions out there that optimal levels and regimes of exercise could fight chronic inflammation while not overstressing the cells. Maybe with our engineered muscle, we can help find out if such notions are true,” Bursac concluded.
Source: Medical Xpress
Journal information: Z. Chen el al., “Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle,” Science Advances (2020). advances.sciencemag.org/lookup … .1126/sciadv.abd9502
