Activated Intestinal Macrophages in Patients with Cirrhosis Release NO and IL-6 that May Disrupt Intestinal Barrier Function

Goode, Elizabeth; Warburton, R; Gelson, William; Watson, Alastair

doi:10.1053/j.gastro.2013.10.031

Cited by 5 publications

(6 citation statements)

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“…Disruption of these barriers is usually associated with a variety of diseases (6,19). Recently, increasing data have verified the dysfunction of intestinal epithelial barrier not only in various cirrhotic animal models but also in patients with chronic liver diseases and cirrhosis (8,10,13,15,18,20,30,31). Intestinal tight junction molecules (occludin, claudin-4, and ZO-1) or adherens junction molecule (E-cadherin) were greatly decreased in the cirrhotic rats.…”

Section: Discussionmentioning

confidence: 98%

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats

Gao

Wen

Tong

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Inflammatory transport through the gut-liver axis may facilitate liver cirrhosis. Cyclooxygenase-2 (COX-2) has been considered as one of the important molecules that regulates intestinal epithelial barrier function. This study was aimed to test the hypothesis that inhibition of COX-2 by celecoxib might alleviate liver cirrhosis via reduction of intestinal inflammatory transport in thiacetamide (TAA) rat model. COX-2/prostaglandin E2 (PGE2)/EP-2/p-ERK integrated signal pathways regulated the expressions of intestinal zonula occludens-1 (ZO-1) and E-cadherin, which maintain the function of intestinal epithelial barrier. Celecoxib not only decreased the intestinal permeability to a 4-kDa FITC-dextran but also significantly increased expressions of ZO-1 and E-cadherin. When celecoxib greatly decreased intestinal levels of LPS, TNF-α, and IL-6, it significantly enhanced T cell subsets reduced by TAA. As a result, liver fibrosis induced by TAA was significantly alleviated in the celecoxib group. These data indicated that celecoxib improved the integrity of intestinal epithelial barrier, blocked inflammatory transport through the dysfunctional gut-liver axis, and ameliorated the progress of liver cirrhosis.

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Section: Discussionmentioning

confidence: 98%

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats

Gao

Wen

Tong

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Intestinal epithelial cells as well as immune cells like antigen presenting cells (for example monocytes [98] and Mφ [99]) are major sources of IL-6 whose secreting mechanisms have been widely reported (refer to Box3 for more interactions between IL-6 and immune cells in the intestine). But studies in mice found that other types of cells including intestinal smooth muscle cells could also secrete IL-6 with the stimuli of IL-1β [100].…”

Section: Il-6 Involved In Lymphocytes Orchestration and Promoting Promentioning

confidence: 99%

Biological characteristics of IL-6 and related intestinal diseases

Guo

Wang

et al. 2021

Int. J. Biol. Sci.

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The intestine serves as an important digestive and the largest immune organ in the body. Interleukin-6(IL-6), an important mediator of various pathways, participates in the interactions between different kinds of cells and closely correlates with intestinal physiological and pathological condition. In this review we summarize the signaling pathways of IL-6 and its functions in maintaining intestinal homeostasis. We also explored its relation with nervous system and highlight its potential role in Parkinson's disease. Based on its specialty of the double-side influences on intestinal tumors and inflammation, we summarize how they are done through distinctive process.

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“…Macrophages secrete NO and pro-inflammatory cytokines in response to bacterial LPS [ 31 ]. NO is a gaseous cellular signaling molecule involved in many inflammatory processes.…”

Section: Resultsmentioning

confidence: 99%

5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

Long

et al. 2016

IJMS

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For the first time, a pale amorphous coumarin derivative, 5-methoxyl aesculetin (MOA), was isolated from the dried bark of Fraxinus rhynchophylla Hance (Oleaceae). MOA modulates cytokine expression in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages, but the precise mechanisms are still not fully understood. We determined the effects of MOA on the production of inflammatory mediators and pro-inflammatory cytokines in the LPS-induced inflammatory responses of RAW 264.7 macrophages. MOA significantly inhibited the LPS-induced production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β. It also effectively attenuated inducible nitric oxide (NO) synthase, cyclooxygenase-2, and TNF-α mRNA expression and significantly decreased the levels of intracellular reactive oxygen species. It inhibited phosphorylation of the extracellular signal-regulated kinase (ERK1/2), thus blocking nuclear translocation of activation protein (AP)-1. In a molecular docking study, MOA was shown to target the binding site of ERK via the formation of three hydrogen bonds with two residues of the kinase, which is sufficient for the inhibition of ERK. These results suggest that the anti-inflammatory effects of MOA in RAW 264.7 macrophages derive from its ability to block both the activation of mitogen-activated protein kinases (MAPKs) and one of their downstream transcription factors, activator protein-1 (AP-1). Our observations support the need for further research into MOA as a promising therapeutic agent in inflammatory diseases.

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Activated Intestinal Macrophages in Patients with Cirrhosis Release NO and IL-6 that May Disrupt Intestinal Barrier Function

Cited by 5 publications

References 0 publications

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats

Inhibition of cyclooxygenase-2 alleviates liver cirrhosis via improvement of the dysfunctional gut-liver axis in rats

Biological characteristics of IL-6 and related intestinal diseases

5-Methoxyl Aesculetin Abrogates Lipopolysaccharide-Induced Inflammation by Suppressing MAPK and AP-1 Pathways in RAW 264.7 Cells

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