Beta-blockers are often used to treat high blood pressure and other cardiovascular diseases. However, in some patients they can trigger or exacerbate psoriasis, an inflammatory skin disease. Scientists at the University of Bonn and Freie Universität Berlin have now found a possible cause for this. Their results have been published in the renowned journal "Autophagy".
It has long been known that beta-blockers can cause severe skin inflammation. However, the cause of this phenomenon was largely unknown until now. The current study sheds light on the matter: It appears that beta-blockers can interfere with the breakdown of defective cell components. In return, the cells release messengers that trigger immune-mediated inflammatory reactions.
At least this is the direction indicated by experiments with cell cultures. The scientists took a close look at an active substance called propranolol. Regardless of the actual mode of action, i. e. the blocking of beta adrenergic receptors, its inflammatory side effects are probably due to a combination of two factors: "Propranolol is both fat-soluble and slightly alkaline," explains Prof. Dr. Günther Weindl from the Pharmaceutical Institute at the University of Bonn.
"Recycling trash bag" in the cell.
Its fat solubility enables the active substance to cross biomembranes - thin, fat-like membranes that enclose cells and some of their components. The second aspect however ensures that propranolol becomes positively charged in an acidic environment. In this state, the substance can no longer return through the membrane.
This combination becomes problematic in a process experts call autophagy. Cells use bubbles from biomembranes as a kind of "recycling trash bag" in which they place defective proteins and other cell components. The bag then later fuses with a second membrane bag, the lysosome. This contains decomposing enzymes that break down the contents of the trash bag and release the individual building blocks back into the cell - perfect recycling.
The liquid in the lysosome is slightly acidic, because the enzymes can only do their work in this environment. Therefore, when a propranolol molecule randomly finds its way through the membrane into the bag, it is positively charged and trapped. Over time, this effect causes more and more propranolol to accumulate in the lysosome.
"And this process apparently disrupts the autophagy," explains Weindl. "This in turn alters a number of processes in the cell. As a result, it releases inflammatory messengers, in particular the so-called interleukin-23, which is mainly secreted by immune cells. The consequence are the observed skin problems."
Not all beta-blockers are problematic
The researchers now hope to further investigate how exactly these processes are related at molecular level. However, their results already indicate that the inflammatory effects occur primarily with fat-soluble beta-blockers. There are in fact substances in this group that are less membrane-permeable. "We tested them in our cell cultures," stresses the pharmacologist. "The interleukin-23 release was significantly lower than after propranolol stimulation."
However, these results still have to be verified in living organisms. It has been known for a long time that dysfunctional autophagy can trigger serious diseases. These include dementia, inflammatory bowel disease and diabetes.
Prof. Dr. Günther Weindl
Pharmaceutical Institute at the University of Bonn
Tel. +49 (0)228-739103
Gerrit Müller, Charlotte Lübow and Günther Weindl: Lysosomotropic beta blockers induce oxidative stress and IL23A production in Langerhans cells. Autophagy DOI: 10.1080/15548627.2019.1686728
Johannes Seiler | idw - Informationsdienst Wissenschaft
Cytoplasm of scrambled frog eggs organizes into cell-like structures, Stanford study finds
07.11.2019 | Stanford Medicine
Sheffield scientists identify new potential treatment pathway for cardiovascular disease
04.11.2019 | University of Sheffield
In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.
An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...
An international research group has observed new quantum properties on an artificial giant atom and has now published its results in the high-ranking journal Nature Physics. The quantum system under investigation apparently has a memory - a new finding that could be used to build a quantum computer.
The research group, consisting of German, Swedish and Indian scientists, has investigated an artificial quantum system and found new properties.
Researchers at the U.S. Department of Energy's (DOE) Argonne National Laboratory have reported a new mechanism to speed up the charging of lithium-ion...
Northwestern University chemists have used visible light and extremely tiny nanoparticles to quickly and simply make molecules that are of the same class as...
Almost everyone uses nanometer-sized alumina these days - this mineral, among others, constitutes the skeleton of modern catalytic converters in cars. Until now, the practical production of nanocorundum with a sufficiently high porosity has not been possible. The situation has changed radically with the presentation of a new method of nanocorundum production, developed as part of a German-Polish cooperation of scientists from Mülheim an der Ruhr and Cracow.
High temperatures and pressures, processes lasting for even dozens of days. Current methods of producing nanometer-sized alumina, a material of significant...
05.11.2019 | Event News
30.10.2019 | Event News
02.10.2019 | Event News
07.11.2019 | Health and Medicine
07.11.2019 | Information Technology
07.11.2019 | Physics and Astronomy