Role of enteric glial cells in inflammatory bowel disease

Abstract

Enteric glial cells (EGCs) represent an extensive but relatively poorly described cell population within the gastrointestinal tract. Accumulating data suggest that EGCs represent the morphological and functional equivalent of CNS astrocytes within the enteric nervous system (ENS). The EGC network has trophic and protective functions toward enteric neurons and is fully implicated in the integration and the modulation of neuronal activities. Moreover, EGCs seem to be active elements of the ENS during intestinal inflammatory and immune responses, sharing with astrocytes the ability to act as antigen-presenting cells and interacting with the mucosal immune system via the expression of cytokines and cytokine receptors. Transgenic mouse systems have demonstrated that specific ablation of EGC by chemical ablation or autoimmune T-cell targeting induces an intestinal pathology that shows similarities to the early intestinal immunopathology of Crohn's disease. EGCs may also share with astrocytes the ability to regulate tissue integrity, thereby postulating that similar interactions to those observed for the blood-brain barrier may also be partly responsible for regulating mucosal and vascular permeability in the gastrointestinal tract. Disruption of the EGC network in Crohn's disease patients may represent one possible cause for the enhanced mucosal permeability state and vascular dysfunction that are thought to favor mucosal inflammation. GLIA 41:81-93, 2003.

Purinergic receptors and gastrointestinal secretomotor function

“…The P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 11 receptors are coupled to stimulation of phospholipase C (PLC). P2Y 12 , P2Y 13 , and P2Y 14 receptors are negatively coupled to adenylyl cyclase (AC); the P2Y 11 receptor is positively coupled to AC. Abbrachio et al [1] provide an update on molecular mechanisms, pathophysiology, and therapeutics of P2Y receptors.…”

“…Antagonists include N6-(2-methylthioethyl)-2-(3,3,3-trifluoropropylthio)-βγ-dichloromethylene-ATP (AR-C6931MX or cangrelor), AZD6140, and active metabolites of clopidogrel and prasugrel. The P2Y 13 receptor is found in nerve cells and immunocytes and is activated similar to the P2Y 12 receptor, but is selectively blocked by 6-(2′-chloro-5-nitro-azophenyl)-pyridoxal-α5-phosphate (MRS2211). The P2Y 14 receptor is activated by UDP-glucose.…”

“…A separate Gs/Gi/AC/ PKA (protein kinase A)/cAMP signaling pathway provides a minor contribution to mechanosensitive 5-HT release [18]. 13 receptors had no effect. Therefore, molecular studies are consistent with pharmacological studies and suggest that dual purinergic modulation of mechanosensory signaling via P2Y 1 and P2Y 12 receptors (that recognize both MRS2179 and 2MeSADP) leads to 5-HT release in EC cells.…”

“…In the guinea pig small intestine, P2Y 4 immunoreactivity is expressed in enteric glial cells (EGCs) in various regions of the GI tract except esophagus. EGCs are important regulators of barrier function, mucosal permeability, neuronal activity, and epithelial cell growth and are active participants in intestinal inflammation [13,95]. Some discrepancy exists between studies on whether P2Y 4 immunoreactivity occurs in epithelial cells, but EGCs may play a role in the modulation of ion transport in gut epithelial cells (for review see [95]).…”

Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation

“…44 In fact, experimental human and animal studies have shown that enteric glial cells may also be involved in intestinal inflammation, 45,46 enteric neurotransmission [47][48][49] and, importantly, are essential for the homeostasis of enteric neurons. 50 With respect to this last aspect, a recent study showed that enteric glia disruption may alter the neurochemical coding of enteric neurons in an experimental animal model.…”