Interferon-gamma depresses human intestinal smooth muscle cell contractility: Relevance to inflammatory gut motility disturbances

Ford, Carey L.; Wang, Yuping; Morgan, Kelli; Boktor, Moheb; Jordan, Paul; Castor, Trevor; Alexander, Jonathan

doi:10.1016/j.lfs.2019.01.059

Cited by 12 publications

(10 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Infiltrating inflammatory cells have been shown to be in close proximity to SMC in the muscular layers and directly affect smooth muscle function by releasing pro‐inflammatory cytokines . In rats, POI decreased jejunal and colonic circular smooth contractions which are associated with decreased gastrointestinal transit linked to increasing pro‐inflammatory cytokines . We also found that decreased α‐SMA in the mouse model could be suppressed by EA, indicating that EA effectively protected SMC function in contraction which may be associated with the anti‐inflammatory effect of EA.…”

Section: Discussionmentioning

confidence: 51%

Effects of electroacupuncture on the intestinal motility and local inflammation are modulated by acupoint selection and stimulation frequency in postoperative ileus mice

Yang

Tian

et al. 2020

Neurogastroenterology Motil

View full text Add to dashboard Cite

Postoperative ileus (POI) is a frequent complication of abdominal surgery characterized by transient hypomotility of the gastrointestinal tract and presents as an inability to tolerate enteral nutrition, nausea, and lack of passage of flatus and stool, along with abdominal distension. 1 Acute early activation of inhibitory neural pathways and secondary late inflammatory responses are considered to be the main pathological mechanisms of POI. 2 This condition accounts for prolonged hospitalization and increased risks of aspiration and infectiousAbstract Background: Electroacupuncture (EA) is widely used in various gastrointestinal diseases around the world, including POI. Here, we investigated different therapeutic effects of EA using lower limb and abdomen acupoints. Methods: Intestinal manipulation was performed in 88 mice, and eight mice underwent a sham operation. Forty mice were randomly divided into model group and four EA groups receiving stimulation at ST36 (2, 10, 30, 100 Hz). The most effective frequency was then used in the following experiments. Forty-eight mice were randomly divided into six groups receiving EA treatment at ST37, ST39, ST25, CV4, CV12, and a non-acupuncture point. Gastrointestinal motility and plasma TNF-α, IL-6 were evaluated in all mice. The local immune response and α-smooth muscle actin (α-SMA) expression were assessed by immunofluorescence, ELISA, and HE staining.Results: ST36 stimulated with 10 or 30 Hz EA significantly increased the gastrointestinal motility and attenuated peripheral inflammation; however, ST36 stimulated with 2 or 100 Hz did not induce any effect. The therapeutic effects on motility and inflammation of 10 Hz EA in the ST36 group were similar in the ST36, ST37, ST39, or CV4 groups, but when applied to ST25, CV12 or non-acupoint had no significant differences. EA at ST36, ST37, ST39, or CV4 significantly inhibited local MPO activity, immune cells infiltration, and increased α-SMA.Conclusions: EA at lower limb and abdomen acupoints with the same stimulation parameters had different therapeutic effects on postoperative dysmotility and inflammation. Furthermore, EA protected SMC to improve gastrointestinal transit by reducing local inflammation in the intestinal musculature in POI. K E Y W O R D Sacupoints, gastrointestinal motility, myeloperoxidase, α-SMA

show abstract

Section: Discussionmentioning

confidence: 51%

Effects of electroacupuncture on the intestinal motility and local inflammation are modulated by acupoint selection and stimulation frequency in postoperative ileus mice

Yang

Tian

et al. 2020

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

“…The mechanism underlying the development and progression of inflammatory bowel disease (IBD) is unclear, but growing evidence suggests that immunological lesions are produced by the infiltration of Th1 cells, which produce inflammatory cytokines [2]. IFNγ is a critical mediator of inflammatory disorders and has been implicated in the pathology of IBD [3,4].…”

Section: Introductionmentioning

confidence: 99%

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

et al. 2022

View full text Add to dashboard Cite

Background: Fibrosis is a common complication of Crohn’s disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype and the EMT process. Methods: Intestinal surgical resections are obtained from control and CD patients with stenotic or penetrating behaviour. Cytokine’s expression, macrophage phenotype, EMT markers and WNT signalling pathway are determined by WB, RT-PCR, ELISA or Cytometry. U937 cells are treated with IFNγ, TNFα, IL1β, IL4 or IL10 and co-cultured with HT29 cells and, in some cases, are treated with XAV939 or miFZD4. The expression of macrophage, EMT and WNT pathway markers in U937 or HT29 cells is analysed by WB or RT-PCR. Results: IFNγ, WNT6, CD16 and CD86 are increased in the intestinal tissue of CD patients. IFNγ-treated U937 activated the EMT process and WNT pathway in HT29 cells, and the EMT process is mediated by FZD4. Conclusions: An IFNγ-rich microenvironment polarises macrophages, which induces EMT through the WNT pathway.

show abstract

“…In mouse ileal smooth muscle (C57BL/6J), IL-1α inhibited intestinal contractile activity via TNF-α-mediated downregulation of CPI-17 [97]. However, Ford et al found that treatment of human intestinal smooth muscle cells with TNF-α did not affect tonic contractions [154]. Furthermore, treatment of rats (Sprague-Dawley) with TNF-α (0.25-0.35 mg/kg for 5 min and function measured 24 h later) did not significantly affect intestinal transit, although there was a synergistic effect of TNF-α and morphine on intestinal permeability [155].…”

Section: Tnf-αmentioning

confidence: 99%

The Role of Inflammatory Mediators in the Development of Gastrointestinal Motility Disorders

Docsa

Sipos

Cox

et al. 2022

IJMS

View full text Add to dashboard Cite

Feeding intolerance and the development of ileus is a common complication affecting critically ill, surgical, and trauma patients, resulting in prolonged intensive care unit and hospital stays, increased infectious complications, a higher rate of hospital readmission, and higher medical care costs. Medical treatment for ileus is ineffective and many of the available prokinetic drugs have serious side effects that limit their use. Despite the large number of patients affected and the consequences of ileus, little progress has been made in identifying new drug targets for the treatment of ileus. Inflammatory mediators play a critical role in the development of ileus, but surprisingly little is known about the direct effects of inflammatory mediators on cells of the gastrointestinal tract, and many of the studies are conflicting. Understanding the effects of inflammatory cytokines/chemokines on the development of ileus will facilitate the early identification of patients who will develop ileus and the identification of new drug targets to treat ileus. Thus, herein, we review the published literature concerning the effects of inflammatory mediators on gastrointestinal motility.

show abstract

Interferon-gamma depresses human intestinal smooth muscle cell contractility: Relevance to inflammatory gut motility disturbances

Cited by 12 publications

References 51 publications

Effects of electroacupuncture on the intestinal motility and local inflammation are modulated by acupoint selection and stimulation frequency in postoperative ileus mice

Effects of electroacupuncture on the intestinal motility and local inflammation are modulated by acupoint selection and stimulation frequency in postoperative ileus mice

IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

The Role of Inflammatory Mediators in the Development of Gastrointestinal Motility Disorders

Contact Info

Product

Resources

About