TY - JOUR
T1 - Anti-TNF-a Therapy exerts intestinal anti-inflammatory and anti-apoptotic effects after massive bowel resection in a rat
AU - Sukhotnik, Igor
AU - Ben-Shahar, Yoav
AU - Pollak, Yulia
AU - Cohen, Shlomi
AU - Guz-Mark, Anat
AU - Shamir, Raanan
N1 - Publisher Copyright:
Copyright © 2020.
PY - 2021/1
Y1 - 2021/1
N2 - Objectives: The aim of this study was to examine the effect of massive small bowel resection on proinflammatory cytokine intestinal expression and the effect of anti-TNF-a antibodies (ATA) on intestinal inflammation, epithelial cell turnover, and intestinal adaptation after bowel resection in rats. Methods: Male Sprague-Dawley rats were divided into 4 experimental groups: Sham-rats underwent bowel transection; Sham-ATA rats underwent bowel transection and were treated with ATA; SBS-animals underwent 75% bowel resection; and SBS-ATA rats underwent bowel resection and were treated with ATA similarly to Group B. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined at sacrifice. TNF-a and apoptosis-related gene and protein levels were determined by Illumina's Digital Gene Expression (DGE) analysis, Real Time PCR, Western blotting, and immunohistochemistry. Results: From 25 genes related to TNF-a signalling that were investigated, 8 genes in the jejunum and 10 genes in the ileum were found to be up-regulated in resected versus sham animals. SBS rats demonstrated a significant increase in tissue and plasma TNF-a, IL-6 levels, intestinal mucosal TNF-a related gene expression, and microscopic parameters of inflammation. Treatment of resected animals with ATA resulted in a significant decrease in TNF-a levels, intestinal mucosal TNF-a-related gene expression, decreased number of intraepithelial lymphocytes and macrophages, and lower apoptotic index compared with SBS animals. Conclusions: In a rat model of SBS, ATA decreased plasma and tissue TNFa levels, diminished mucosal inflammation, and inhibited cell apoptosis.
AB - Objectives: The aim of this study was to examine the effect of massive small bowel resection on proinflammatory cytokine intestinal expression and the effect of anti-TNF-a antibodies (ATA) on intestinal inflammation, epithelial cell turnover, and intestinal adaptation after bowel resection in rats. Methods: Male Sprague-Dawley rats were divided into 4 experimental groups: Sham-rats underwent bowel transection; Sham-ATA rats underwent bowel transection and were treated with ATA; SBS-animals underwent 75% bowel resection; and SBS-ATA rats underwent bowel resection and were treated with ATA similarly to Group B. Parameters of intestinal adaptation, enterocyte proliferation, and apoptosis were determined at sacrifice. TNF-a and apoptosis-related gene and protein levels were determined by Illumina's Digital Gene Expression (DGE) analysis, Real Time PCR, Western blotting, and immunohistochemistry. Results: From 25 genes related to TNF-a signalling that were investigated, 8 genes in the jejunum and 10 genes in the ileum were found to be up-regulated in resected versus sham animals. SBS rats demonstrated a significant increase in tissue and plasma TNF-a, IL-6 levels, intestinal mucosal TNF-a related gene expression, and microscopic parameters of inflammation. Treatment of resected animals with ATA resulted in a significant decrease in TNF-a levels, intestinal mucosal TNF-a-related gene expression, decreased number of intraepithelial lymphocytes and macrophages, and lower apoptotic index compared with SBS animals. Conclusions: In a rat model of SBS, ATA decreased plasma and tissue TNFa levels, diminished mucosal inflammation, and inhibited cell apoptosis.
KW - Adaptation
KW - Apoptosis
KW - Intestinal inflammation
KW - Proliferation
KW - Short bowel syndrome
KW - TNF-a
UR - http://www.scopus.com/inward/record.url?scp=85098673958&partnerID=8YFLogxK
U2 - 10.1097/MPG.0000000000002876
DO - 10.1097/MPG.0000000000002876
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C2 - 32740515
AN - SCOPUS:85098673958
SN - 0277-2116
VL - 72
SP - 49
EP - 55
JO - Journal of Pediatric Gastroenterology and Nutrition
JF - Journal of Pediatric Gastroenterology and Nutrition
IS - 1
ER -
