A group of researchers, including almost a dozen from UC San Diego, announced Thursday that they may have found a method of treating certain chronic inflammatory diseases by disposing of damaged mitochondria, the powerhouse of the cell.
Inflammation is a natural biological response to eliminate foreign irritants in the body, but can harm healthy cells when not kept in check.
Inflammation is generally regulated in the body by a molecule called the NLRP3 inflammasome, which triggers an inflammatory response when a cell’s mitochondria is damaged or attacked.
Overactive NLRP3 inflammasomes can lead to certain inflammatory diseases like gout, osteoarthritis and fatty liver disease. In a study of mice, UCSD researchers were able to circumvent this issue by using an enzyme inhibitor to force cells to begin their waste removal process, mitophagy, to eliminate damaged mitochondria before a cells’ NLRP3 inflammasome can be activated.
The researchers published their study in Thursday’s issues of the journal Cell Metabolism. Their previous research also revealed that damaged mitochondria trigger NLRP3 inflammasome response.
“After that, we wondered if we could reduce harmful excess inflammation by intentionally inducing mitophagy, which would eliminate damaged mitochondria and should in turn pre-emptively inhibit NLRP3 inflammasome activation,” said pharmacology and pathology professor Michael Karin, the study’s senior author. “But at the time we didn’t have a good way to induce mitophagy.”
The enzyme treatment reduced the mice’s acute inflammation, caused by uric acid, and reversed inflammation associated with a genetic disorder known as Muckle-Well Syndrome.
The researchers found that the enzyme treatment works to quell the release of two pro-inflammatory molecules, interleukin-1 beta and interleukin-18. Some drugs that are currently on the market can block IL-1 beta but not IL- 18, but the use of the enzyme inhibitor blocked both.
“There are several diseases, including lupus and osteoarthritis, whose treatment likely will require dual inhibition of both IL-1 (beta) and IL-18,” Karin said.
Karin, first author Elsa Sanchez-Lopez and researchers from UCSD, completed the study with researchers from the University of Texas at Austin and the Hospital Universitario Fuenlabrada in Madrid, Spain.
— City News Service
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