Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-α activation

Abstract

Because of its lack of toxicity, its ability in reducing inflammation and its selective PPARα action, PEA might be an innovative molecule to broaden pharmacological strategies against UC.

Emerging roles for enteric glia in gastrointestinal disorders

“…Using optical clearing methods combined with high-resolution confocal microscopy in the human jci.org Volume 125 Number 3 March 2015 glial cells. In Ppara knockout mice, PEA has no anti-inflammatory effects and does not reduce S-100β or TLR4 expression (or that of other inflammatory markers) (62,68). While in this study PEA was given exogenously, it is produced naturally in the gut and its levels are regulated by the enzyme fatty acid amide hydrolase, whose expression has been proposed to be important in the control of intestinal inflammation (69).…”

“…Enteric glia express TLRs, and these are differentially upregulated in response to pathogenic and non-pathogenic bacteria (61,62). When the upregulation of TLRs by a bacterial pathogen occurs, it leads to NF-κB activation.…”

“…They also extend the earlier observations of enhanced expression in Crohn's disease and raise the possibility that enteric glia upregulate MHC class II in response to specific pathogens as part of the host defense mechanisms to protect the ENS. The links between inflammation and enteric glial activation were recently tested in a mouse model of intestinal inflammation and using human colonic biopsies (62). In dextran sodium sulphate-induced colitis and human ulcerative colitis, the lipid mediator palmitoylethanolamide (PEA) reduced inflammation through activation of PPARα (62).…”

“…The links between inflammation and enteric glial activation were recently tested in a mouse model of intestinal inflammation and using human colonic biopsies (62). In dextran sodium sulphate-induced colitis and human ulcerative colitis, the lipid mediator palmitoylethanolamide (PEA) reduced inflammation through activation of PPARα (62). It also reduced enteric glial S-100B expression, the expression of TLR4 and the production of NO in the animal model and in isolated human and mouse enteric This study and a more recent study by Seelig et al (73) demonstrate that misfolded prion protein can be transmitted from the brain to the gut, where it can cause pathological changes in enteric glia and neurons.…”

Inflammation and Chronic Pelvic Pain: A Biological Trigger for Depression in Women?

“…PEA, an endogenous fatty acid amide, is a congener of the endocannabinoid anandamide belonging to a class of lipid mediators, the family of N-acylethanolamines. PEA has been reported to reduce pain behaviors, and to inhibit somatosensory activation and correlated events in different models of pelvic inflammation [87][88][89][90][91][92][93][94][95][96][97]. Moreover, PEA exerted an antidepressant-like effect comparable to the reference drug fluoxetine [98,99] (Table 2).…”