Protein Associated With Inflammation Surprisingly Repairs Common CF Mutation

Researchers at Institut national de la santé et de la recherche médicale (INSERM) in France have learned one way to “fix” cells that have characteristics of cystic fibrosis. These cells, which had faulty CFTR channel proteins, were able to make more functional CFTR protein following treatment with tumor necrosis factor alpha (TNF-α).

Dr. Sara Bitam, lead author of the study entitled “An Unexpected Effect of TNF-α on F508del-CFTR Maturation and Function,” which was published in F1000Research, found the results of the team’s research just that: unexpected. Although cystic fibrosis is regarded as causing inflammation in the lungs and TNF-α is typically associated with causing inflammation, the researchers found that a 10-minute exposure of TNF-α to the faulty cells in CF patients had a healing effect.

In the study, the researchers began with cells expressing genes with the F508del-CFTR mutation and human bronchial cells of primary origin that express the F508del-CFTR mutation. Both of these cells served as in vitro models of cystic fibrosis. After growing these cells and noticing a poor current of chloride ions through the CFTR channel proteins, the researchers applied TNF-α to the cells for 10 minutes.

Following exposure to TNF-α, the cells were able to produce functional CFTR channel proteins that increased chloride current. In fact, the cells sustained CFTR expression and function for at least 24 hours. This was attributed to downstream actions of TNF-α, in which another protein called protein kinase C (PKC) allowed for CFTR to insert into the plasma membrane and function correctly.

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Other individuals are excited about these results, as well. “These findings are an exciting development in the bid to find a cure for cystic fibrosis – a devastating disease that affects many thousands of people worldwide,” said Rebecca Lawrence, Managing Director of F1000Research, in a news release.

“We hope to investigate whether TNF-α is linked to the severity of cystic fibrosis; if so then TNF-α levels might be one of a panel of molecules that could be used as a prognostic marker in the disease,” said Dr. Aleksander Edelman, principal investigator on the study. These could be important next steps for the research team.