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Research Article
Masatoshi Hori
The University of Tokyo
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6804-2288
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This work is licensed under a CC BY 4.0 License. Read Full License
Postoperative ileus (POI) is gastrointestinal motility dysfunction after abdominal surgery caused by mechanical stress to intestine. It occurs nausea and vomiting, and lead to lower QOL during hospitalization for patients. It is regarded as a problem because it costs medical expenses due to long hospitalization. The intestinal inflammation caused by macrophage and neutrophil is thought to be important of the mechanism of POI. In tissue injury or inflammation, adenosine triphosphate (ATP) is released from injured cell. Purinergic P2X7 receptor (P2X7R) is expressed on inflammatory cells and ATP induces the secretion of inflammatory mediators through P2X7R. P2X7R antagonist is thought to be important in the first step of inflammation, and it is confirmed that P2X7R antagonist showed anti-inflammatory effects in chemically-induced colitis models. Therefore, we hypothesized that P2X7R has important function in POI and examined the effect of P2X7R antagonist in mouse POI model. As a result, P2X7R antagonist A438079 ameliorated macrophage and neutrophil infiltration in POI. The impairment of intestinal transit was improved by P2X7R antagonist. It tended to ameliorate the increase of IL-6, IL-1β and TNF-α mRNA expression in intestinal muscularis caused by POI. P2X7R expressed on both infiltrated and resident macrophages in the inflamed ileal muscle layer. In conclusion, P2X7R antagonist showed the anti-inflammatory effect through P2X7R on macrophages, and it may be the target to treat POI.
Keywords
P2X7 receptor, anti-inflammation, postoperative ileus, macrophages
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Masatoshi Hori
The University of Tokyo
Corresponding Author
ORCiD: https://orcid.org/0000-0002-6804-2288
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 11 May, 2021
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Postoperative ileus (POI) is gastrointestinal motility dysfunction after abdominal surgery caused by mechanical stress to intestine. It occurs nausea and vomiting, and lead to lower QOL during hospitalization for patients. It is regarded as a problem because it costs medical expenses due to long hospitalization. The intestinal inflammation caused by macrophage and neutrophil is thought to be important of the mechanism of POI. In tissue injury or inflammation, adenosine triphosphate (ATP) is released from injured cell. Purinergic P2X7 receptor (P2X7R) is expressed on inflammatory cells and ATP induces the secretion of inflammatory mediators through P2X7R. P2X7R antagonist is thought to be important in the first step of inflammation, and it is confirmed that P2X7R antagonist showed anti-inflammatory effects in chemically-induced colitis models. Therefore, we hypothesized that P2X7R has important function in POI and examined the effect of P2X7R antagonist in mouse POI model. As a result, P2X7R antagonist A438079 ameliorated macrophage and neutrophil infiltration in POI. The impairment of intestinal transit was improved by P2X7R antagonist. It tended to ameliorate the increase of IL-6, IL-1β and TNF-α mRNA expression in intestinal muscularis caused by POI. P2X7R expressed on both infiltrated and resident macrophages in the inflamed ileal muscle layer. In conclusion, P2X7R antagonist showed the anti-inflammatory effect through P2X7R on macrophages, and it may be the target to treat POI.
Figure 1
Figure 2
Figure 3
Figure 4
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