Researchers at the Robert Bosch Hospital (RBK) and the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology (IKP) in Stuttgart have now deciphered a new mechanism of action of the human immune system that protects against intestinal bacteria and pathogenic yeasts. The internationally renowned scientific journal Nature presents their findings.
"This completely new biological principle is particularly important in terms of inflammation and disease," said the head of the research group, PD Dr. Jan Wehkamp, who is funded by the German Research Foundation (DFG) as part of the Emmy Noether Programme of financial support for young researchers. Dr. Wehkamp has made a major new discovery relating to a human protein (defensin) that activates antibiotics and is produced in lower quantities in people suffering from inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. The reduction in the number of defensins blocks the immunological defence against fungi and bacteria, and eventually leads to a weakening of the antimicrobial barrier, which is seen as as the major cause of inflammation. These findings were obtained in close cooperation with the Department of Internal Medicine I led by Prof. Dr. Eduard F. Stange at the Robert Bosch Hospital. The team of researchers believes that the newly deciphered mechanism of action might contribute to the development of new therapies for treating inflammatory and infectious diseases. The finding was presented by the internationally renowned scientific journal "Nature" (Nature, DOI: 10.1038/nature09674, online access for subscribers at www.nature.com).
The interdisciplinary team of researchers investigated how defensins, a group of antibiotics naturally produced by the human body, act under low-oxygen conditions. Prior to the investigations, defensins had habitually been tested in the presence of oxygen, despite the limited quantities of oxygen that are actually present in the human intestine. In their investigations, the researchers chose to take a completely different approach. The doctoral student Björn Schröder and his colleagues found out that the human beta defensin-1 (hBD-1) unfolds a strong antibiotic activity against lactic acid bacteria and yeast under low-oxygen conditions. In addition, the researchers discovered that another human protein, thioredoxin, is able to activate beta defensin-1 even in the presence of oxygen.
Although the antibiotic hBD-1, which belongs to the group of defensins and is naturally produced by the human body, is permanently being produced by all human epithelial surfaces, its actual function had not previously been clarified. The current investigations now suggest that hBD-1 protects human epithelia against beneficial intestinal bacteria such as lactic acid bacteria as well as exerting a positive effect in the defence against pathogenic yeasts.
Original publication:Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, Buchner J, Schaller M, Stange EF, Wehkamp J. "Reduction of disulfide bonds unmasks potent antimicrobial activity of human β-defensin 1”, Nature, DOI: 10.1038/nature09674
Further information:PD Dr. med. Jan WehkampHead of workgroup funded under the Emmy Noether Programme of the German Research FoundationDr. Margarete Fischer-Bosch Institute for Clinical PharmacologyRobert Bosch Hospital, Internal Medicine IAuerbachstraße 11270376 StuttgartTel.: +49 (0)711/8101-5700Fax: +49 (0)711/859295