Inflammation pathways

David M. Phillips / Photo Researchers, Inc

To uncover the inflammatory pathways involved in cell injury and death, Kenneth Rock at the University of Massachusetts and colleagues injected necrotic cells into mice deficient in various toll-like receptors and found that neutrophilic inflammatory response was not significantly reduced. ¹ Using the same strategy in interleukin-1 (IL-1) receptor-deficient mice, along with mice with induced liver damage in situ, they found that the IL-1 pathway was required for the inflammatory response triggered by dead and injured cells.

"It's one of the first [studies] to really start looking at the molecular basis of the recognition of dying self-cells," says David Kranz, immunology researcher at the University of Illinois, and a member of the Faculty of 1000. Surprisingly, Kranz says, toll-like receptors, Tlr2 and Tlr4, which are critical in inflammatory responses to infection, were not key players in the inflammatory pathways involved in cell injury.

"Maybe now we can use that knowledge to prevent damage from acute inflammation," in conditions such as heart attacks and ischemia, Kranz says. Pharmaceutical companies are already interested in blocking the IL-1 pathway but "maybe the interest will be stepped up even further because of this paper," he adds.

These papers were selected from multiple disciplines from the Faculty of 1000, a web-based literature awareness tool (www.f1000biology.com).