n-Butyrate inhibits Jun NH(2)-terminal kinase activation and cytokine transcription in mast cells.
Mast cells are well known to contribute to type I allergic conditions but only recently have been brought in association with chronic relapsing/remitting autoimmune diseases such as celiac disease and ulcerative colitis. Since the bacterial metabolite n-butyrate is considered to counteract intestinal inflammation we investigated the effects of this short chain fatty acid on mast cell activation. Using RNAse protection assays and reporter gene technology we show that n-butyrate downregulates TNF-alpha transcription. This correlates with an impaired activation of the Jun NH(2)-terminal kinase (JNK) but not other MAP kinases such as ERK and p38 that are largely unaffected by n-butyrate. As a consequence, we observed a decreased nuclear activity of AP-1 and NF-AT transcription factors. These results indicate that n-butyrate inhibits critical inflammatory mediators in mast cells by relatively selectively targeting the JNK signalling.
Diakos
Christos
C
Institute of Immunology, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
Prieschl
Eva E
EE
Säemann
Marcus D
MD
Böhmig
Georg A
GA
Csonga
Robert
R
Sobanov
Yury
Y
Baumruker
Thomas
T
Zlabinger
Gerhard J
GJ
D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004789:Enzyme Activation; D007249:Inflammation; D048031:JNK Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002087:Butyrates; D016207:Cytokines; D050778:NFATC Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4