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!
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences