Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Research uncovers signaling pathways related to brain-immune system links

Cell biology studies may lay groundwork for a novel HIV treatment

New research on signaling pathways in immune cells bolsters evidence of connections between the central nervous system and the immune system. The findings may also advance the scientific foundation for a potential HIV treatment that may block the virus that causes AIDS.

The cell culture study by a research team from The Children’s Hospital of Philadelphia and the University of Pennsylvania appears in the Proceedings of the National Academy of Sciences, published online on May 4.

The team, led by Steven D. Douglas, M.D., chief of the Section of Immunology at The Children’s Hospital of Philadelphia, analyzed neurokinin-1 receptors found on the surfaces of monocytes, immune cells that develop into macrophages. The neurokinin-1 receptors (NK-1R) are docking sites for substance P, a well-known neurotransmitter that plays important roles in both immune function and the nervous system.

In the current study, the Douglas team investigated two forms of NK-1R in a human monocyte/macrophage cell line. One was a full-length receptor, the other a shortened version with fewer amino acids. When the researchers added substance P to cell cultures with the receptors, both responded with an increase in calcium ions, but used distinct signaling pathways.

The truncated NK-IR did not respond directly to substance P, but worked through another signaling molecule, the chemokine RANTES, to increase the calcium flow. The RANTES molecule is important because it binds to another cell receptor, CCR5, which is crucial in allowing common strains of HIV (R5 strains) to infect immune cells.

Significantly, when the investigators added the drug aprepitant, which binds to NK-1R, to their cell cultures, it inhibited signaling from both the full-length and short form of the receptors.

Although the current study was not focused on HIV infection, it directly relates to broader interests of Dr. Douglas’ laboratory. He currently leads a four-year program project grant from the National Institute of Mental Health, entitled, "Neurokinin-1R (Substance P Receptor) Antagonists for HIV Therapy." One project within that grant will conduct a phase 1 (safety) trial of aprepitant in adults with HIV infection. Currently used as an anti-nausea medication, aprepitant, which has the trade name Emend, might also block HIV infection.

Because macrophages are a reservoir for HIV, a strategy that denies the virus entry into those immune cells may be important in combating HIV infection. Dr. Douglas showed in 2001 that another NK-1R antagonist blocked HIV replication within macrophages in cell culture. The hope is that aprepitant may show a similar protective effect in patients.

"We postulate that blocking NK-1R may send signals to turn off the CCR5 receptor for HIV, closing the door to the virus," said Dr. Douglas. "Underlying the signaling mechanisms are the questions, ’how does the immune system talk to the nervous system?’ and ’how does the nervous system talk back?’ Substance P is a link between both systems, and this study increases our understanding of those underlying questions."

John Ascenzi | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Chimpanzees Shed Light on Origins of Human Walking
09.10.2015 | Stony Brook University

nachricht In “Cell”: Floppy but fast
09.10.2015 | Heidelberger Institut für Theoretische Studien gGmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Reliable in-line inspections of high-strength automotive body parts within seconds

Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.

To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...

Im Focus: Kick-off for a new era of precision astronomy

The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.

As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...

Im Focus: Locusts at the wheel: University of Graz investigates collision detector inspired by insect eyes

Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.

Inspired by insects

Im Focus: Physicists shrink particle accelerator

Prototype demonstrates feasibility of building terahertz accelerators

An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...

Im Focus: Simple detection of magnetic skyrmions

New physical effect: researchers discover a change of electrical resistance in magnetic whirls

At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

Navigating the unknown

09.10.2015 | Information Technology

New Artificial Cells Mimic Nature’s Tiny Reactors

09.10.2015 | Materials Sciences

Chimpanzees Shed Light on Origins of Human Walking

09.10.2015 | Life Sciences

More VideoLinks >>>