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New findings in innate immunity may lead to treatments for atherosclerosis

Bethesda, MD Scientists are one step closer to deciphering the molecular signaling process controlling innate immunity with the discovery that a molecule called IRAK1 regulates the expression of the anti-inflammatory cytokine IL-10. Because atherosclerosis patients often have elevated IL-10 levels, IRAK1 may be a viable target for developing therapeutics for atherosclerosis.

The research appears as the "Paper of the Week" in the December 3 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Innate immunity is the body's first response to infection, and it plays a major role in regulating infection, inflammation, cell growth, and apoptosis. During an innate immune reaction, macrophages, dendritic cells, and epithelial cells use a set of transmembrane receptors called Toll-like receptors (TLRs) to initiate signaling cascades.

"TLRs can sense diverse environmental cues and send signals downstream to a family of interleukin-1 receptor associated kinases (IRAKs). These IRAKs then activate and/or regulate specific cytokine gene expression," explains Dr. Liwu Li of the Wake Forest University School of Medicine.

However, the specificity of the TLR signaling process is not clearly understood. "In the past," says Dr. Li, "it was thought that all IRAKs may play a somewhat redundant role in regulating the nuclear transcription factor NFκB and the expression of pro-inflammatory cytokines such as IL-1beta and TNFalpha." However, mice that lack IRAK1 can still activate NFκB, suggesting that IRAK1 may be involved in other activities.

Dr. Li and his colleagues discovered that IRAK1 actually activates a molecule called Signal Transducer and Activator of Transcription 3, or Stat3, which in turn activates expression of the anti-inflammatory cytokine IL-10. The scientists also found that IRAK1 can translocate into the nucleus and regulate the nuclear transcription of p
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Contact: Nicole Kresge
nkresge@asbmb.org
301-634-7415
American Society for Biochemistry and Molecular Biology
26-Nov-2004


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