Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New findings in innate immunity may lead to treatments for atherosclerosis

26.11.2004


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 NFêB and the expression of pro-inflammatory cytokines such as IL-1beta and TNFalpha." However, mice that lack IRAK1 can still activate NFêB, 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 proteins. "Our finding sets IRAK1 apart from other IRAKs and elucidates a novel pathway in innate immunity regulation," says Dr. Li.

Because atherosclerosis patients usually have elevated serum IL-10 levels, the scientists also looked at IRAK1 levels in blood from atherosclerosis patients. They found that IRAK1 is modified and localized to the nucleus in these patients, indicating a possible link between IRAK1 regulation and the pathogenesis of atherosclerosis. "Inflammation and infection have been increasingly shown to play a significant role in the pathogenesis and/or resolution of atherosclerosis," explains Dr. Li. "Anti- inflammatory cytokines such as IL-10 may serve as a self protective mechanism to prevent excessive inflammation and contribute to plaque stability. Indeed, patients with higher IL-10 serum levels have a better chance of recovery. Therefore, elevated IRAK1 modification and IL-10 levels observed in atherosclerosis patients may be a compensatory and self-protective mechanism."

Manipulating innate immunity may eventually be a therapeutic strategy for treating atherosclerosis. "Our study, as well as others, indicates that innate immunity alteration plays a critical role in either the pathogenesis or resolution of atherosclerosis. IRAK1 may provide a viable target for developing therapeutic interventions for atherosclerosis. Compounds or strategies directed at preventing or enhancing IRAK1 modification and nuclear entry may hold great promise in treating atherosclerosis," concludes Dr. Li.

Besides atherosclerosis, alterations in innate immunity can cause diabetes, cancer, and numerous other inflammatory disorders. Further understanding of the innate immunity process may lead to development of therapies for these diseases as well.

Nicole Kresge | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo

nachricht Full of hot air and proud of it
18.04.2018 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>