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'Dead' gene comes to life, puts chill on inflammation, Stanford researchers find
Date:7/23/2013

STANFORD, Calif. A gene long presumed dead comes to life under the full moon of inflammation, Stanford University School of Medicine scientists have found.

The discovery, described in a study to be published July 23 in eLife, may help explain how anti-inflammatory steroid drugs work. It also could someday lead to entirely new classes of anti-inflammatory treatments without some of steroids' damaging side effects.

Chronic inflammation plays a role in cancer and in autoimmune, cardiovascular and neurodegenerative diseases, among others. Anti-inflammatory steroid drugs are widely prescribed for treating the inflammatory states that underlie or exacerbate these conditions.

"Inflammation tells your body something is wrong," said the study's senior author, Howard Chang, MD, PhD, professor of dermatology at Stanford and the recipient of an early career scientist award from the Howard Hughes Medical Institute. "But after it does its job of alerting immune cells to a viral or bacterial infection or spurring them to remove debris from a wound site, it has to get turned off before it causes harm to healthy tissue."

That appears to be what the "undead" gene does. Chang's team, which identified it, has named it Lethe, after the stream in Greek mythology that makes the deceased who cross it forget their pasts.

The master regulator of inflammation inside cells a bulky complex of several proteins, collectively called NF-kappa-B is a transcription factor: It can switch on hundreds or even thousands of genes in a cell's nucleus. When aroused by signals at the cell surface (typically delivered by circulating proteins or microbial components), NF-kappa-B activates pro-inflammatory genes, gearing that cell up to combat viral or bacterial assaults and respond to an injury.

Lethe, which the investigators found is activated by NF-kappa-B, subdues the master regulator's massive influence on the genome, curtailing the infla
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Contact: Bruce Goldman
goldmanb@stanford.edu
650-725-2106
Stanford University Medical Center
Source:Eurekalert

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