Original ResearchFull Report: Basic and Translational—Alimentary TractShort-Chain Fatty Acids Activate GPR41 and GPR43 on Intestinal Epithelial Cells to Promote Inflammatory Responses in Mice
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Animals
All experiments with animals in this study were approved by the Purdue Animal Care and Use Committee. C57BL/6 mice were from Harlan Laboratories (Indianapolis, IN). CD45.1 C57BL/6 mice were from The Jackson Laboratory (Bar Harbor, ME). GPR43−/− C57BL/6 mice were from Deltagen (San Mateo, CA), and GPR41−/− C57BL/6 mice were described previously.14
Induction of Intestinal Inflammation with Ethanol and TNBS
Mice were starved overnight and received 100 μL 50% ethanol in the rectum using a round-tip needle. Intestinal inflammation with TNBS was induced as
Mice Deficient With GPR41 or GPR43 Are Defective in Mounting the Normal Inflammatory Response After an Ethanol-Induced Breach of the Gut Barrier Function
To determine the functions of SCFAs and their receptors in regulation of acute antibacterial responses, we temporarily breached the gut barrier function through rectal administration of ethanol into WT, GPR41−/−, and GPR43−/− mice. As expected, the ethanol treatment induced a transient decrease in the weight of WT mice at 24 h after the treatment (Figure 1A). However, the 2 knockout (KO) mouse strains were significantly less affected by the treatment. Gross examination revealed that only WT
Discussion
The mechanism of action for probiotics, prebiotics, and SCFAs to promote immunity in the gut is incompletely understood.29 We studied the roles of SCFA receptors in regulating immune responses in the intestine. The results identified positive roles of SCFAs and their receptors in preparing ECs to promptly mount immune responses during immunological challenges.
Our study demonstrated that SCFA signals are required for mounting acute inflammatory responses in the colon after ethanol treatment.
Acknowledgments
The authors thank B. Ulrich and F. Chu (Purdue University) for their excellent assistance and Dr. B. Vallance (University of British Columbia) for providing a C rodentium strain.
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Author names in bold designate shared co-first authorship.
Conflicts of interest The authors disclose no conflicts
Funding This study was supported, in part, from grants from National Institutes of Health (R01AI074745, R01DK076616, 1R01AI080769 and 1S10RR028293) and National Multiple Sclerosis Society to CHK.
The microarray data is deposited at: http://www.ncbi.nlm.nih.gov/geo (GSE36569).