Anti-inflammatory properties of the μ opioid receptor support its use in the treatment of colon inflammation

Abstract

The physiologic role of the μ opioid receptor (MOR) in gut nociception, motility, and secretion is well established. To evaluate whether MOR may also be involved in controlling gut inflammation, we first showed that subcutaneous administration of selective peripheral MOR agonists, named DALDA and DAMGO, significantly reduces inflammation in two experimental models of colitis induced by administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) or peripheral expansion of CD4+ T cells in mice. This therapeutic effect was almost completely abolished by concomitant administration of the opioid antagonist naloxone. Evidence of a genetic role for MOR in the control of gut inflammation was provided by showing that MOR-deficient mice were highly susceptible to colon inflammation, with a 50% mortality rate occurring 3 days after TNBS administration. The mechanistic basis of these observations suggests that the anti-inflammatory effects of MOR in the colon are mediated through the regulation of cytokine production and T cell proliferation, two important immunologic events required for the development of colon inflammation in mice and patients with inflammatory bowel disease (IBD). These data provide evidence that MOR plays a role in the control of gut inflammation and suggest that MOR agonists might be new therapeutic molecules in IBD

The endogenous cannabinoid system protects against colonic inflammation

“…The endogenous opioidergic system was recently shown to participate in the protection against inflammation in the TNBS model of colitis through the activation of µ-opioid receptors (34). To test whether the protective functions of the endogenous cannabinoid system involve the activation of endogenous opioid signaling, we analyzed Enk mRNA-expressing neurons in untreated and DNBS-treated colons derived from both CB1 +/+ and CB1 -/-mice.…”

Hemorphins Act as Homeostatic Agents in Response to Endotoxin-Induced Stress

“…/CaM/calcineurin/ NFAT pathway with MOR function [24]. The MOR was reported to exert anti-inflammatory properties, and MOR agonists were claimed to be new therapeutic molecules for treating autoimmune and inflammatory diseases [50]. b-endorphin, as anti-inflammatory neuropeptides and MOR agonists, down regulates the inflammatory processes by shifting Th1/Th2 balance towards Th2 [51].…”

No Evidence for an Involvement of the P38 and JNK Mitogen-Activated Protein in Inflammatory Bowel Diseases

“…Colonic specimens were removed to score macroscopic and microscopic inflammation, and to quantify myeloperoxidase (MPO), TNF-α, IL-1-β mRNA, and MAPKs activity 50% NaCl 0.9%/50% ethanol ( Fig. 1) [15,16]. Control mice received a mixture of 50% NaCl 0.9%/50% ethanol using the same technique.…”

“…Protein preparation and immunoblotting were performed as described [16]. Total protein extracts were obtained by homogenization of colon samples in a PBS lysis buffer containing 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, and a protease inhibitor cocktail.…”

“…Total protein extracts were obtained by homogenization of colon samples in a PBS lysis buffer containing 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, and a protease inhibitor cocktail. Total proteins (50 µg/sample) were separated by PAGE and electroblotted [16]. Immunodetection of MPO was performed with an overnight incubation of the immunoblotted membrane with a rabbit polyclonal primary antibody (dilution 1:500; DAKO, Trappes, France) at 4 • C. Additionally, a swine secondary peroxidase-conjugated antibody (dilution 1:1,000; DAKO) was added for 1 hour at room temperature.…”