Details

Autor(en) / Beteiligte

• Bachmann, Malte
• Meissner, Carlotta
• Pfeilschifter, Josef
• Mühl, Heiko

Titel

Cooperation between the bacterial‐derived short‐chain fatty acid butyrate and interleukin‐22 detected in human Caco2 colon epithelial/carcinoma cells

Ist Teil von

• BioFactors (Oxford), 2017-03, Vol.43 (2), p.283-292

Ort / Verlag

Netherlands

Erscheinungsjahr

2017

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• 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