Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus

Buchholz, Bettina M.; Shapiro, Richard A.; Vodovotz, Yoram; Billiar, Timothy R.; Sodhi, Chhinder P.; Hackam, David J.; Bauer, Anthony J.

doi:10.1152/ajpgi.00211.2014

Cited by 6 publications

(8 citation statements)

References 28 publications

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“…Data on myocyte TLR4 function in the setting of endotoxic ileus has demonstrated that non-hematopoietic, non-enterocyte intestinal TLR4 signaling can cause both enteric and systemic inflammation. (34) Given these findings, it is essential to understand the primary source of TLR4 signaling in the intestine after SBR. This information will be critical for future targeting of drug therapies to the appropriate TLR4 receptors.…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis

Barron

Bao

Aladegbami

et al. 2017

Journal of Pediatric Surgery

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Background A significant number of children with short bowel syndrome experience intestinal failure-associated liver disease. We recently demonstrated accelerated hepatic steatosis after 50% small bowel resection (SBR) in mice. Since SBR is associated with alterations in the gut microbiome, the purpose of this study was to determine whether TLR4 signaling is critical to the development of resection associated hepatic steatosis. Methods Male C57BL6 (control) and TLR4-knockout (KO) mice underwent 50% proximal SBR. Liver sections were analyzed to obtain the percent lipid content, and Ileal sections were assessed for morphological adaptation. Intestinal TLR4 mRNA expression was measured at 7 days and 10 weeks. Results Compared to controls, TLR4 KO mice demonstrated similar weight gain and morphological adaptation after SBR. Hepatic steatosis was decreased 32-fold in the absence of TLR4. Intestinal TLR4 mRNA expression was significantly elevated 7 days after SBR. We also found that TLR4 expression in the intestine is 20-fold higher in whole bowel compared with isolated enterocytes. Conclusions TLR4 signaling is critical for the development of resection-associated steatosis, but not involved in intestinal adaptation after massive SBR. Further studies are needed to delineate the mechanism for TLR4 signaling in the genesis of resection-associated liver injury.

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Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis

Barron

Bao

Aladegbami

et al. 2017

Journal of Pediatric Surgery

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“…CXCL1 is also important in normal bowel function. Various diseases, such as endotoxemia [171], brain injury [172] and severe injury trauma [173], are associated with an increase in CXCL1 levels in either the blood or the gut. This leads to a decrease in contraction amplitude in the ileum [173], which results in feeding intolerance and ileus.…”

Section: Ileum and Contraction Amplitudementioning

confidence: 99%

The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs

Korbecki

Szatkowska

Kupnicka

et al. 2022

IJMS

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CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary glands, stomach, liver, pancreas, intestines, and kidneys). We focus on the importance of CXCL1 on implantation and placentation as well as on human pluripotent stem cells. We also show the significance of CXCL1 in selected diseases of the abdominal organs, including the gastrointestinal tract and oral cavity (periodontal diseases, periodontitis, Sjögren syndrome, Helicobacter pylori infection, diabetes, liver cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), HBV and HCV infection, liver ischemia and reperfusion injury, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), obesity and overweight, kidney transplantation and ischemic-reperfusion injury, endometriosis and adenomyosis).

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“…In a mouse model of sepsis (BALB/c), gene expression profiling showed that the IL-17 pathway was associated with decreased contraction amplitude and frequency (24 and 48 h) and the blockade of IL-17A (IP injection with IL-17A antibody) improved motility in a cecal ligation and puncture model of sepsis [146]. Buchholz et al also found that IL-17 was associated with late rodent ileus (24 h, C57BL/6) [147]. In a traumatic brain injury rat (SD) model, increased IL-17, along with IL-1α and β, was associated with slowed intestinal transit [148].…”

Section: Il-17mentioning

confidence: 99%

“…The role of CXCL1 in the gut has been mostly studied in the context of inflammatory or infectious diseases. However, CXCL1 is upregulated in animal models of ileus and inhibits intestinal contractile activity in mice and rats [24,147,173]. In addition, CXCL1 was significantly higher in trauma patients who developed ileus compared to trauma patients with no slowed motility [24].…”

Section: Other Inflammatory Mmediators and Signaling Pathwaysmentioning

confidence: 99%

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

Docsa

Sipos

Cox

et al. 2022

IJMS

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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.

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Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus

Abstract: Buchholz BM, Shapiro RA, Vodovotz Y, Billiar TR, Sodhi CP, Hackam DJ, Bauer AJ. Myocyte TLR4 enhances enteric and systemic inflammation driving late murine endotoxic ileus.

Cited by 6 publications

References 28 publications

Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis

Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis

The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs

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

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