In this Issue
August 2016; volume 311, issue 2
Neurogastroenterology and Motility
- Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig
This article provides a detailed characterization of the μ-opioid receptor (MOR) in the enteric nervous system of the guinea pig. The distribution of MOR within neurochemically defined neuronal subtypes is correlated with the established physiological effects of MOR agonists. The ability of clinically and experimentally relevant MOR ligands to induce endocytosis of MOR in enteric neurons is also examined, with key differences in the kinetics and magnitude of internalization observed between agonists.
Stem Cells, Tissue Engineering, Development, and Cancer
- Hepatocyte nuclear factor 4α is required for cell differentiation and homeostasis in the adult mouse gastric epithelium
The transcription factor (TF) HNF4α is known to be expressed in stomach, but its function was unknown. We show here that inducing deletion of HNF4α caused increased proliferation and collapse of chief cell endoplasmic reticulum (ER) and secretory architecture. We show HNF4α binds and upregulates the known ER-regulating TF XBP1. As we have previously shown XBP1 governs expression of the TF MIST1, we now show chief cell maturation depends on a HNF4α→XBP1→MIST1 transcriptional sequence.
Liver and Biliary Tract Physiology/Pathophysiology
Inflammation, Immunity, and Infection
- Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes
The secondary bile acid, ursodeoxycholic acid (UDCA), specifically inhibits TNF-α-induced release of the proinflammatory cytokine, IL-8, from monocytes. The effects of the bile acid appear to be mediated by inhibition of TRAF-2-mediated NFκB activation and subsequent downregulation of IL-8 mRNA expression. Such actions of UDCA would serve to dampen mucosal immune responses in vivo, suggesting it may provide an alternative approach to the current use of biologics for prevention of TNF-α-induced inflammation in IBD patients.