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Protein finding could lead to treatment for inflammatory diseases

A protein that undesirably shields a skin poxvirus from the immune system may become the key ingredient in a new topical treatment for inflammatory diseases, say medical researchers at the University of Illinois at Urbana-Champaign.

In a study appearing this month in the Journal of Virology, the scientists revealed both the function of the protein (MC160) and how it works on a molecular level to inhibit inflammatory responses.

MC160 is so named because it was the 160th gene of the molluscum contagiosum virus (MCV) sequence. "This is a really important protein for a couple of reasons," said Joanna L. Shisler, a professor of microbiology in the U. of I. College of Medicine at Urbana-Champaign who studies poxviruses.

"MC160 first piqued our curiosity because it has a homologue in humans and in herpes viruses, and each of these homologues regulate NF-kappaB" she said. NF-kB is a cellular transcription factor that activates the expression of genes involved in inflammation. Shisler's lab was interested in determining whether MC160 also acted on NF-kB.

In their study -- funded by the National Institutes of Health -- Shisler and Daniel Brian Nichols, a doctoral student in microbiology, treated human embryonic kidney cells with cytokines known to activate NF-kB. Cytokines are chemicals made by immune cells that boost the immune system by stimulating inflammation to fight infectious pathogens.

"We found that the NF-kB levels were always lower in MC160-expressing cells," Shisler said. "This was an exciting new finding because no one had previously found a function for MC160. Currently, Brian and I think that this protein's role is to inhibit NF-kB activation in MCV-infected skin cells, to prevent cytokines from boosting the immune system. MC160 is probably helping the virus persist."

Upon further examination, Shisler and Nichols discovered that MC160 shuts down the NF-kB-triggered inflammatory response by degrading a subunit of t
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Source:University of Illinois at Urbana-Champaign


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