242 - Bile Acid-Induced Activation of ERK/Sphingosine Kinase 2 Contributes to Intestinal Inflammation and Barrier Dysfunction in Multi-Drug Resistance 2 Gene Deficient Mice

2018 ◽  
Vol 154 (6) ◽  
pp. S-1078
Author(s):  
Runping Liu ◽  
Xiaojiaoyang Li ◽  
Eric Kwong ◽  
Michael Hinton ◽  
Huiping Zhou
Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3206
Author(s):  
Kemp M. Anderson ◽  
Christopher P. Gayer

The Farnesoid-X Receptor, FXR, is a nuclear bile acid receptor. Its originally described function is in bile acid synthesis and regulation within the liver. More recently, however, FXR has been increasingly appreciated for its breadth of function and expression across multiple organ systems, including the intestine. While FXR’s role within the liver continues to be investigated, increasing literature indicates that FXR has important roles in responding to inflammation, maintaining intestinal epithelial barrier function, and regulating immunity within the gastrointestinal (GI) tract. Given the complicated and multi-factorial nature of intestinal barrier dysfunction, it is not surprising that FXR’s role appears equally complicated and not without conflicting data in different model systems. Recent work has suggested translational applications of FXR modulation in GI pathology; however, a better understanding of FXR physiology is necessary for these treatments to gain widespread use in human disease. This review aims to discuss current scientific work on the role of FXR within the GI tract, specifically in its role in intestinal inflammation, barrier function, and immune response, while also exploring areas of controversy.


Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1454-1458 ◽  
Author(s):  
Barbara Zemann ◽  
Bernd Kinzel ◽  
Matthias Müller ◽  
Roland Reuschel ◽  
Diana Mechtcheriakova ◽  
...  

FTY720, a potent immunomodulatory drug in phase 2/3 clinical trials, induces rapid and reversible sequestration of lymphocytes into secondary lymphoid organs, thereby preventing their migration to sites of inflammation. As prerequisite for its function, phosphorylation of FTY720 to yield a potent agonist of the sphingosine-1-phosphate receptor S1P1 is required in vivo, catalyzed by an as-yet-unknown kinase. Here, we report on the generation of sphingosine kinase 2 (SPHK2) knockout mice and demonstrate that this enzyme is essential for FTY720 phosphate formation in vivo. Consequently, administration of FTY720 does not induce lymphopenia in SPHK2-deficient mice. After direct dosage of FTY720 phosphate, lymphopenia is only transient in this strain, indicating that SPHK2 is constantly required to maintain FTY720 phosphate levels in vivo.


Hepatology ◽  
2015 ◽  
Vol 61 (4) ◽  
pp. 1216-1226 ◽  
Author(s):  
Masayuki Nagahashi ◽  
Kazuaki Takabe ◽  
Runping Liu ◽  
Kesong Peng ◽  
Xiang Wang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document