Newly found protein might put the brakes on rheumatoid arthritis

Scientists have discovered how an antimicrobial peptide produced by neutrophils also acts as a “molecular brake” to prevent runaway inflammation—a finding that suggests that therapies based on these peptides could help to treat autoimmune disorders such as rheumatoid arthritis, according to a study published online April 4, 2016 in Proceedings of the National Academy of Sciences.

“This discovery opens the door to new approaches for the treatment and prevention of chronic inflammation. We are hopeful that with further research, these treatments could be exploited in the near future,” said study co-author Mohini Gray, PhD, MBBS, Principal Investigator at the MRC Centre for Inflammation Research at University of Edinburgh, in Edinburgh, Scotland.

This finding also paves the way for peptide-based therapeutics that combine both anti-inflammatory and antimicrobial properties into a single drug, the authors predicted.

In prior research, the scientists found that these peptides—alpha defensins—diminished inflammation and also decreased the bacterial load in mice infected with pathogens. But what the study didn’t show was how alpha defensins actually do this.

For this study, the researchers wanted to find out how this process works. In in vitro experiments with human cells, they determined that apoptotic neutrophils release the alpha defensins. The proteins then enter macrophages and significantly inhibit protein translation but without inducing the unfolded-protein response or affecting mRNA stability.

“This is, to our knowledge, the first demonstration of a peptide released from one cell type (neutrophils) directly regulating mRNA translation in another (macrophages),” the authors concluded. “By preventing protein translation, [the alpha defensing] functions as a “molecular brake” on macrophage-driven inflammation, ensuring both pathogen clearance and the resolution of inflammation with minimal bystander tissue damage.”

These findings could lead to new treatments for chronic inflammatory disorders including rheumatoid arthritis, the researchers said. Such therapies could even prevent arthritis from flaring up in the first place, they predicted.