Collaboration between Research Teams of Gerhard Zlabinger and Diana Mechtcheriakova.
Recent article of Kovarik Johannes (research group of Gerhard Zlabinger, Institute of Immunology) as a result of collaboration and complementation of scientific expertizes and novel methodological approaches between research teams within our Center.
Eicosanoid modulation by the short-chain fatty acid n-butyrate in human monocytes.
Kovarik JJ, Hölzl MA, Hofer J, Waidhofer-Söllner P, Sobanov Y, Koeffel R, Saemann MD, Mechtcheriakova D, Zlabinger GJ. Immunology. 2013 Feb 11. doi: 10.1111/imm.12089. [Epub ahead of print] PMID: 23398566
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n-Butyrate deriving from bacterial fermentation in the mammalian intestine is a key determinant in gastrointestinal homeostasis. Since its presence is largely restricted to the gastrointestinal tract and immunological features of this region have striking similarities to the effects brought about by this physiologically occurring substance there is great interest in its molecular mode of action, which, so far has been poorly understood. To examine the effects of this short-chain fatty acid and/or TLR2 and TLR4 engagement on inflammatory- associated pathways in human monocytes, a 180-gene signature of immunity/inflammation-associated genes was assembled based on the knowledge-driven approach of innate immune cell biology and inflammatory process data mining. This signature contained targets involved in immune response and inflammation, and included many upstream signalling molecules (kinases and phosphatases in hierarchical levels), transcription factors, and the downstream chemokines and cytokines. PTGS2 (also known as COX-2), a key enzyme in biosynthesis of prostanoids, and other molecules central to eicosanoid signalling were as well included to the array. In this study, the data-driven, n-butyrate-affected eicosanoid-associated gene network was delineated using the Ingenuity Pathway Analysis (IPA) Software; core analysis was used to identify the most significantly affected biological processes.
The results of the current study propose the modulation of the expression of eicosanoid pathway-related genes after microbial activation and concomitant interference with n-butyrate. Among many other mediators of eicosanoid signalling n-butyrate massively induces PGE2 production by increasing the expression of PTGS2 (COX-2) in monocytes following TLR-4 and TLR-2 activation and induces secretion of LTB4 and TXB2. This underscores the role of n-butyrate as a crucial mediator of gut specific immunity.
Link zu Pubmed