Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kovarik, JJ; Hölzl, MA; Hofer, J; Waidhofer-Söllner, P; Sobanov, Y; Koeffel, R; Saemann, MD; Mechtcheriakova, D; Zlabinger, GJ.
Eicosanoid modulation by the short-chain fatty acid n-butyrate in human monocytes.
Immunology. 2013; 139(3):395-405
Doi: 10.1111/imm.12089
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- Co-Autor*innen der Med Uni Graz
- Köffel René
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- Abstract:
- n-Butyrate deriving from bacterial fermentation in the mammalian intestine is a key determinant in gastrointestinal homeostasis. We examined the effects of this short-chain fatty acid and Toll-like receptor 2 (TLR) and TLR4 engagement on inflammatory/immunity-associated genes, cyclo-oxygenases (COXs), prostaglandins (PGs) and leukotrienes (LTs) in human monocytes. Before RNA isolation, freshly isolated human monocytes were co-incubated for different time-points with 1 mm n-butyrate alone or in combination with bacterial stimuli. Based on a knowledge-driven approach, a signature of 180 immunity/inflammation-associated genes was picked and real-time PCR analysis was performed. Pathway analysis was carried out using a web-based database analysing program. Based on these gene expression studies the findings were evaluated at the protein/mediator level by Western blot analysis, FACS and ELISA. Following co-incubation with n-butyrate and lipopolysaccharide, key enzymes of the eicosanoid pathway, like PTGS2 (COX-2), TXS, ALOX5, LTA4H and LTC4S, were significantly up-regulated compared with stimulation with lipopolysaccharide alone. Furthermore, release of the lipid mediators PGE(2), 15d-PGJ(2), LTB(4) and thromboxane B(2) was increased by n-butyrate. Regarding signalling, n-butyrate had no additional effect on mitogen-activated protein kinase and interfered differently with early and late phases of nuclear factor-κB signalling. Our results suggest that among many other mediators of eicosanoid signalling n-butyrate massively induces PGE(2) production by increasing the expression of PTGS2 (COX-2) in monocytes following TLR4 and TLR2 activation and induces secretion of LTB(4) and thromboxane B(2). This underscores the role of n-butyrate as a crucial mediator of gut-specific immunity.
- Find related publications in this database (using NLM MeSH Indexing)
- Butyrates - metabolism
- Cyclooxygenase 2 - genetics
- Dinoprostone - biosynthesis
- Eicosanoids - genetics
- Gene Expression Profiling -
- Gene Expression Regulation - immunology
- Humans -
- Leukotriene B4 - genetics
- Lipopolysaccharides - immunology
- Monocytes - immunology
- Real-Time Polymerase Chain Reaction - methods
- Thromboxane B2 - genetics
- Toll-Like Receptor 2 - genetics
- Toll-Like Receptor 4 - genetics
- Up-Regulation - immunology
- Find related publications in this database (Keywords)
- eicosanoids
- gene regulation
- monocytes
- n-butyrate