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Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates  More>>
Authors:
Singh, Udai P.; Singh, Narendra P.; [1]  Singh, Balwan; [2]  Price, Robert L.; [3]  Nagarkatti, Mitzi; [1]  Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu [1] 
  1. Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29208 (United States)
  2. National Primate Research Center, Emory University, Atlanta GA 30329 (United States)
  3. Department of Cell and Developmental Biology, University of South Carolina, Columbia, SC 29208 (United States)
Publication Date:
Jan 15, 2012
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 258; Journal Issue: 2; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; DEXTRAN; DISEASES; INFLAMMATION; LARGE INTESTINE; LYMPH NODES; LYMPHOKINES; MACROPHAGES; MAST CELLS; MICE; NATURAL KILLER CELLS; NEUTROPHILS; RECEPTORS; SODIUM SULFATES
OSTI ID:
22215219
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; CODEN: TXAPA9; Other: PII: S0041-008X(11)00434-0; TRN: US12R3795036182
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2011.11.005
Submitting Site:
USN
Size:
page(s) 256-267
Announcement Date:
Apr 12, 2014

Citation Formats

Singh, Udai P., Singh, Narendra P., Singh, Balwan, Price, Robert L., Nagarkatti, Mitzi, and Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2011.11.005.
Singh, Udai P., Singh, Narendra P., Singh, Balwan, Price, Robert L., Nagarkatti, Mitzi, & Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu. Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis. United States. doi:10.1016/J.TAAP.2011.11.005.
Singh, Udai P., Singh, Narendra P., Singh, Balwan, Price, Robert L., Nagarkatti, Mitzi, and Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu. 2012. "Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis." United States. doi:10.1016/J.TAAP.2011.11.005. https://www.osti.gov/servlets/purl/10.1016/J.TAAP.2011.11.005.
@misc{etde_22215219,
title = {Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10{sup −/−} mice by attenuating the activation of T cells and promoting their apoptosis}
author = {Singh, Udai P., Singh, Narendra P., Singh, Balwan, Price, Robert L., Nagarkatti, Mitzi, and Nagarkatti, Prakash S., E-mail: Prakash.Nagarkatti@uscmed.sc.edu}
abstractNote = {Inflammatory bowel disease (IBD) is a chronic intestinal inflammation caused by hyperactivated effector immune cells that produce pro-inflammatory cytokines. Recent studies have shown that the cannabinoid system may play a critical role in mediating protection against intestinal inflammation. However, the effect of cannabinoid receptor induction after chronic colitis progression has not been investigated. Here, we investigate the effect of cannabinoid receptor-2 (CB2) agonist, JWH-133, after chronic colitis in IL-10{sup −/−} mice. JWH-133 effectively attenuated the overall clinical score, and reversed colitis-associated pathogenesis and decrease in body weight in IL-10{sup −/−} mice. After JWH-133 treatment, the percentage of CD4{sup +} T cells, neutrophils, mast cells, natural killer (NK1.1) cells, and activated T cells declined in the intestinal lamina propria (LP) and mesenteric lymph nodes (MLN) of mice with chronic colitis. JWH-133 was also effective in ameliorating dextran sodium sulfate (DSS)-induced colitis. In this model, JWH-133 reduced the number and percentage of macrophages and IFN-γ expressing cells that were induced during colitis progression. Treatment with aminoalkylindole 6-iodo-pravadoline (AM630), a CB2 receptor antagonist, reversed the colitis protection provided by JWH-133 treatment. Also, activated T cells were found to undergo apoptosis following JWH-133 treatment both in-vivo and in-vitro. These findings suggest that JWH-133 mediates its effect through CB2 receptors, and ameliorates chronic colitis by inducing apoptosis in activated T cells, reducing the numbers of activated T cells, and suppressing induction of mast cells, NK cells, and neutrophils at sites of inflammation in the LP. These results support the idea that the CB2 receptor agonists may serve as a therapeutic modality against IBD. -- Highlights: ► JWH-133, a cannnabinoid receptor-2 agonist ameliorates experimental colitis. ► JWH-133 suppressed inflammation and toxicity to colon by inducing T cell apoptosis. ► JWH-133 decreased mast cells, macrophages, NK cells, IFN-γ{sup +} cells in the LPL. ► AM630, a cannnabinoid receptor-2 antagonist inverted the colitis defense of JWH-133. ► Cannnabinoid receptor-2 may serve as a novel therapeutic target for IBD.}
doi = {10.1016/J.TAAP.2011.11.005}
journal = {Toxicology and Applied Pharmacology}
issue = {2}
volume = {258}
journal type = {AC}
place = {United States}
year = {2012}
month = {Jan}
}