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Single microRNA fine-tunes innate immune response
Date:2/19/2008

ulate gene expression.) By knocking out Mefc2, the authors found that some of the effects caused by microRNA-223 were eliminated.

The researchers demonstrated that mice modified to lack microRNA-223 expression had up to three times as many granulocytes in their bone marrow and blood. Moreover, the granulocytes matured more rapidly and then reacted more aggressively to stimuli. This increased activity caused tissue inflammation and damage within the lungs with age or, in an acute inflammation model, within the liver, muscle and kidneys.

If you have an infection in the lungs, granulocytes will migrate to the site of the infection and attack, says Jonathan Johnnidis, first author of the paper and a former technician in the Camargo lab, and now a graduate student in molecular biology at the University of Pennsylvania. Once the infection is cleared granulocytes usually migrate away and settle down. However, in this case they didnt stand down after they were done fighting. Instead they continued an inflammatory response that did more damage.

Like a hand grenade once you pop the trigger out, these granulocytes are going to explode, regardless of whether they are surrounded by healthy tissue or harmful bacteria, adds Camargo. Lack of microRNA-223 makes it much easier to activate the grenade.

Camargo plans to further investigate the effect of this microRNA on disease. Our work suggests that microRNA-223 physiologically fine-tunes both the generation and function of granulocytic cells, delimiting their production and preventing excessive activation, he says. Also, since many forms of leukemia express diminished levels of microRNA-223, we are investigating how silencing of this microRNA may contribute to the development of that disease.


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Contact: Cristin Carr
carr@wi.mit.edu
617-324-0460
Whitehead Institute for Biomedical Research
Source:Eurekalert

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