Alterations in the gut barrier and involvement of Toll‐like receptor 4 in murine postoperative ileus

Lin, Sisi; Zhang, R.-Q.; Shen, Li; Xu, Xiaobin; Li, K.; Bazhin, Alexandr V.; Fichna, Jakub; Li, Y.-Y.

doi:10.1111/nmo.13286

Cited by 11 publications

(25 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with earlier ndings, we observed a signi cant increase in the levels of pro-in ammatory cytokines in the blood of POI animals 10,29 . These in ammatory mediators contribute to the decreased GI motility associated with POI through various mechanisms such as direct cytotoxic effects and induction of nitricoxide (NO) and prostanoid production 30 .…”

Section: Discussionsupporting

confidence: 92%

“…POI increases the risk of postoperative complications and morbidity 3 . Recent studies have shown that postoperative in ammatory reactions are involved in the development of POI 10,13,14 . Consistently with earlier reports 6,7 , at 24 and 48 h after intestinal manipulation, we observed a signi cant decrease in GI transit rate, induction of an in ammatory response characterized by leukocyte in ltration in the intestinal tissue, villous epithelial cell structural damage, submucosal edema, hyperemia, and epithelial cell necrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, macrophages are potently activated by bacterial cell wall molecules (such as LPS) which interact with Toll-like receptors (TLRs) to promote in ammatory responses 23 . As intestinal permeability is transiently increased following intestinal manipulation, bacterial translocation may represent another potential mechanism by which resident macrophages can be stimulated 10,24 . Manipulation of the intestine triggers the in ux of leukocytes in manipulated intestinal segments, impairing the contractile properties of the in amed intestine 25 .…”

Section: Discussionmentioning

confidence: 99%

“…POI was induced using a small bowel manipulation method as previously reported 10,11 . In brief, mice were anesthetized via intraperitoneal injection of 2% chloral hydrate at a dose of 0.15ml/10g, and the abdomen was shaved and sterilized with 75% ethanol.…”

Section: 1animal Studiesmentioning

confidence: 99%

“…Intestinal motility was evaluated 24h and 48h after surgery 10 . Brie y, mice were gavaged with a charcoal marking mixture (10% charcoal suspension in 10% gum arabic, 0.1 ml per 10 g of body weight) (Sigma-Aldrich Co., St. Louis, MO).…”

Section: Evaluation Of Intestinal Motilitymentioning

confidence: 99%

See 4 more Smart Citations

Traditional Chinese medicine Da-Cheng-Qi-Tang ameliorates impaired gastrointestinal motility and intestinal inflammatory response in a mouse model of postoperative ileus

Chen

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Chinese medicine decoction Da-Cheng-Qi-Tang (DCQT) is effective for treating gastrointestinal (GI) disorders, including postoperative ileus (POI); however, the mechanism by which DCQT improves intestinal motility of POI remains unknown. Purpose The aim of this study is to explore the therapeutic effect and mechanism of the decoction with the traditional formula DCQT (T-DCQT) and a modified DCQT (M-DCQT) in an experimental POI mouse model. Methods Mice were divided into 5 experimental groups with 16 mice per group as follows: (1) control group; (2) sham group; (3) POI group; (4) T-DCQT group and (5) M-DCQT group. Each group was subdivided into 2 groups in which the therapeutic effect was examined at 24h and 48h after operation. POI was induced by classic intestinal manipulation operation and the gastrointestinal(GI) motility was measured with a charcoal marking mixture gavage. The intestinal tissues were collected for evaluation of the histopathological alteration, and analysis of the expression of inflammatory signal pathways, as NF-κB, p38 MAPK, and TLR4 by qPCR, immunohistochemical staining and western-blotting, respectively. Plasma inflammatory cytokines were determined using a high-throughput liquid chip. All analyses were performed with samples collected 24 and/or 48h after operation. Results GI transit was significantly reduced in mice with POI and this dysfunction was alleviated after administration of either T-DCQT or M-DCQT enema. When compared to controls, the pathological changes in the ileum mucosal of POI mice were significantly improved, and the increased expression of NF-κB, p38 MAPK, and TLR4 in the intestinal tissues were reversed, following T- DCQT or M-DCQT treatment. Plasma inflammatory cytokines, such as IL-1α, IL-6, MCP-1, MIP-1β and IL-17 levels were significantly highly expressed in POI group, and most of them, as IL-1α, IL-6, MIP-1β and IL-17 were significantly reduced after T-DCQT or M-DCQT treatment. Conclusion The current study indicated that administration of T-DCQT or M-DCOT could ameliorate the POI-associated inflammatory response and improve GI motility, by controlling inflammatory cytokines release and modulating the expression of some inflammatory signal pathways in the POI mouse model.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: 1animal Studiesmentioning

confidence: 99%

Section: Evaluation Of Intestinal Motilitymentioning

confidence: 99%

See 3 more Smart Citations

Traditional Chinese medicine Da-Cheng-Qi-Tang ameliorates impaired gastrointestinal motility and intestinal inflammatory response in a mouse model of postoperative ileus

Chen

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Alterations of the Rectal Microbiome Are Associated with the Development of Postoperative Ileus in Patients Undergoing Colorectal Surgery

Shogan

Chen

Duchalais

et al. 2020

Journal of Gastrointestinal Surgery

View full text Add to dashboard Cite

IL-1-dependent enteric gliosis guides intestinal inflammation and dysmotility and modulates macrophage function

et al. 2022

View full text Add to dashboard Cite

Muscularis Externa Macrophages (ME-Macs) and enteric glial cells (EGCs) are closely associated cell types in the bowel wall, and important interactions are thought to occur between them during intestinal inflammation. They are involved in developing postoperative ileus (POI), an acute, surgery-induced inflammatory disorder triggered by IL-1 receptor type I (IL1R1)-signaling. In this study, we demonstrate that IL1R1-signaling in murine and human EGCs induces a reactive state, named enteric gliosis, characterized by a strong induction of distinct chemokines, cytokines, and the colony-stimulating factors 1 and 3. Ribosomal tagging revealed enteric gliosis as an early part of POI pathogenesis, and mice with an EGC-restricted IL1R1-deficiency failed to develop postoperative enteric gliosis, showed diminished immune cell infiltration, and were protected from POI. Furthermore, the IL1R1-deficiency in EGCs altered the surgery-induced glial activation state and reduced phagocytosis in macrophages, as well as their migration and accumulation around enteric ganglia. In patients, bowel surgery also induced IL-1-signaling, key molecules of enteric gliosis, and macrophage activation. Together, our data show that IL1R1-signaling triggers enteric gliosis, which results in ME-Mac activation and the development of POI. Intervention in this pathway might be a useful prophylactic strategy in preventing such motility disorders and gut inflammation.

show abstract

Alterations in the gut barrier and involvement of Toll‐like receptor 4 in murine postoperative ileus

Cited by 11 publications

References 54 publications

Traditional Chinese medicine Da-Cheng-Qi-Tang ameliorates impaired gastrointestinal motility and intestinal inflammatory response in a mouse model of postoperative ileus

Traditional Chinese medicine Da-Cheng-Qi-Tang ameliorates impaired gastrointestinal motility and intestinal inflammatory response in a mouse model of postoperative ileus

Alterations of the Rectal Microbiome Are Associated with the Development of Postoperative Ileus in Patients Undergoing Colorectal Surgery

IL-1-dependent enteric gliosis guides intestinal inflammation and dysmotility and modulates macrophage function

Contact Info

Product

Resources

About