title: Cooperation between the bacterial-derived short-chain fatty acid butyrate and interleukin-22 detected in human Caco2 colon epithelial/carcinoma cells.
abstract: By generating biologically active factors luminal microbiota shape the intestinal micro-milieu thereby regulating pathological processes such as inflammation and carcinogenesis. Preclinical data suggest that bacterial-derived butyrate and the signal transducer and activator of transcription (STAT)-3 activating cytokine interleukin (IL)-22 display concordant protective properties at the inflamed colonic epithelium. Herein, biochemical cooperation between the short-chain fatty acid butyrate and IL-22 was investigated by focusing on human Caco2 colon epithelial/carcinoma cells. We report that physiological levels of butyrate enhance IL-22 signaling thereby enforcing expression of the prototypic STAT3-downstrean target genes α1-antichymotrypsin and suppressor of cytokine signaling (SOCS)-3. A dual mode of butyrate action on the IL-22/STAT3 axis was identified. Butyrate acted by upregulating IL-22R1, the decisive chain of the heterodimeric IL-22 receptor, and, independent from that, has the potential to directly amplify STAT3-mediated gene activation as detected by chromatin immunoprecipitation analysis of STAT3 binding to the SOCS3 promoter. Since trichostatin A acted similarly, inhibition of histone deacetylases is likely at the root of these butyrate biological properties. The mutual benefit gained from interactions between the host and commensal intestinal bacteria-derived factors is an expanding field of research beginning to affect clinical practice. Data presented herein propose a supportive and fine-tuning role for butyrate in IL-22 signaling that might be therapeutically exploited by local butyrate administration or by increasing its bacterial production in the context of a fiber-rich diet. © 2016 BioFactors, 43(2):283-292, 2017.
authors: Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany.
authors: Malte
authors: M
authors: Bachmann
authors: Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany.
authors: Carlotta
authors: C
authors: Meissner
authors: Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany.
authors: Josef
authors: J
authors: Pfeilschifter
authors: Pharmazentrum Frankfurt/ZAFES, University Hospital Goethe-University Frankfurt, 60590 Frankfurt am Main, Germany.
authors: Heiko
authors: H
authors: Mühl
mesh_terms: D002087:Butyrates / Q000378:metabolism; D018938:Caco-2 Cells; D063646:Carcinogenesis / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000382:microbiology / Q000628:therapy; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000628:therapy; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005227:Fatty Acids / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D064307:Microbiota / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D002087:Butyrates; D005227:Fatty Acids; D007378:Interleukins; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22
keywords: butyrate; interleukin-22; suppressor of cytokine signaling-3; α1-antichymotrypsin