PMID- 23844009
OWN - NLM
STAT- MEDLINE
DCOM- 20140207
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 7
DP  - 2013
TI  - The dual effect of cannabinoid receptor-1 deficiency on the murine postoperative 
      ileus.
PG  - e67427
LID - 10.1371/journal.pone.0067427 [doi]
LID - e67427
AB  - INTRODUCTION: Intestinal inflammatory responses play a critical role in the 
      pathogenesis of postoperative ileus (POI). As cannabinoid receptor-1 (CB1) is 
      involved in inhibiting gastrointestinal (GI) motility and anti-inflammation, we 
      aimed to explore its contribution to POI. METHODS: Experimental POI was induced 
      in adult female CB1-deficient (CB1-/-) mice and wild-type littermates (C57BL/6N) 
      by standardized small bowel manipulation. Twenty-four hours after surgery, GI 
      transit was assessed by charcoal transport. FITC avidin, F4/80, and 
      myeloperoxidase immunohistochemistry techniques were used to evaluate the 
      inflammatory response in the muscularis of ileum and colon. Expressions of 
      p38MAPK and its phosphorylated form (pp38) in the intestine were determined. 
      Plasma levels of proinflammatory cytokines and chemokines were measured by ELISA 
      as well. RESULTS: POI was characterized by decreased GI transit (p<0.01) and 
      accompanied by a marked intestinal and systematic inflammatory response in 
      wild-type and CB1-/- mice. Increased numbers of inflammatory cells, including 
      macrophages, neutrophils, and mast cells were observed in the muscularis of ileum 
      and colon (p<0.01, or p<0.05). Plasma levels of interleukin-6 (IL-6), 
      cytokine-induced neutrophil chemoattractant-1 (CINC-1/KC), and monocyte 
      chemoattractant protein-1 (MCP-1) were elevated (p<0.01, or p<0.05). Expression 
      of p38 and pp38 increased in the intestine (p<0.01, or p<0.05). CB1-/- mice 
      showed an increased inflammatory response during POI, especially the systemic 
      inflammatory markers, such as IL-6, KC, CINC1, and pp38 expression were increased 
      as compared to those in WT mice (p<0.05). CONCLUSIONS: Intestinal motility was 
      inhibited during POI. In this condition, inhibition of motility did not seem to 
      be altered by the absence of CB1 receptors, however, an increased inflammatory 
      response was observed in CB1-/- mice. Hence, CB1 receptor activation rather than 
      inhibition may reduce the inflammatory response in POI, which has a remote 
      potential to relate into reduced inhibition of intestinal motility during POI.
FAU - Li, Yong-yu
AU  - Li YY
AD  - Department of Pathophysiology, Institute of Digestive Disease, Tongji University 
      School of Medicine, Shanghai, China. liyongyu@tongji.edu.cn
FAU - Cao, Ming-hua
AU  - Cao MH
FAU - Goetz, Brigitte
AU  - Goetz B
FAU - Chen, Chun-qiu
AU  - Chen CQ
FAU - Feng, Ya-jing
AU  - Feng YJ
FAU - Chen, Chang-Jie
AU  - Chen CJ
FAU - Kasparek, Michael S
AU  - Kasparek MS
FAU - Sibaev, Andrej
AU  - Sibaev A
FAU - Storr, Martin
AU  - Storr M
FAU - Kreis, Martin E
AU  - Kreis ME
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130703
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-6)
RN  - 0 (Receptor, Cannabinoid, CB1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/blood
MH  - Colon/metabolism/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Gastrointestinal Motility/genetics
MH  - Ileum/metabolism/pathology
MH  - Ileus/*genetics/metabolism
MH  - Interleukin-6/blood
MH  - Macrophages/metabolism/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Smooth/metabolism/pathology
MH  - Postoperative Complications/*genetics/metabolism
MH  - Postoperative Period
MH  - Receptor, Cannabinoid, CB1/*deficiency/genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/blood
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3701010
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/07/12 06:00
MHDA- 2014/02/08 06:00
PMCR- 2013/07/03
CRDT- 2013/07/12 06:00
PHST- 2013/01/10 00:00 [received]
PHST- 2013/05/19 00:00 [accepted]
PHST- 2013/07/12 06:00 [entrez]
PHST- 2013/07/12 06:00 [pubmed]
PHST- 2014/02/08 06:00 [medline]
PHST- 2013/07/03 00:00 [pmc-release]
AID - PONE-D-13-01586 [pii]
AID - 10.1371/journal.pone.0067427 [doi]
PST - epublish
SO  - PLoS One. 2013 Jul 3;8(7):e67427. doi: 10.1371/journal.pone.0067427. Print 2013.