Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature

Pijls, Kirsten; Jonkers, Daisy; Elamin, Elhaseen; Masclee, Ad; Koek, Ger H.

doi:10.1111/liv.12271

Cited by 109 publications

(112 citation statements)

References 154 publications

(230 reference statements)

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“…In fact, previous findings from our laboratory identified the role of cocaine-mediated ROS in endothelial barrier dysfunction, which, in turn, contributes to leaky blood-brain barrier (31). Furthermore, ROS is also implicated as a mediator of epithelial injury, as it is known to impair several epithelial cell functions via elicitation of signal cascades (32,33). Our findings clearly demonstrate that exposure of L2 alveolar epithelial cells to cocaine resulted in a time-dependent induction of NADPH oxidase-dependent ROS and mROS, which was critical for cocaine-mediated disruption of barrier permeability.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

Lü

Chen

Simet

et al. 2016

Am J Respir Cell Mol Biol

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Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell-substrate impedance sensing and FITCdextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1a. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2-related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1a/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1a and PDGF-BB. Pharmacological blocking of HIF-1a significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

Lü

Chen

Simet

et al. 2016

Am J Respir Cell Mol Biol

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“…Several risk factors have been postulated for the increased susceptibility to infections in liver disease including alterations in gut microbiota, impaired gut motility and enhanced gut permeability promoting bacterial translocation [2], and immune dysfunction. Cirrhosis-associated immune dysfunction emanates from deficiencies in both adaptive and innate immune systems encompassing a complex array of reticuloendothelial system dysfunction, impaired monocyte activation and cytokine secretion, decreased neutrophil mobilization and phagocytic activity, impaired leucocyte function, and low complement levels [3].…”

Section: Introductionmentioning

confidence: 99%

Early invasive fungal infections and colonization in patients with cirrhosis admitted to the intensive care unit

Theocharidou

Agarwal

Jeffrey

et al. 2016

Clinical Microbiology and Infection

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Bacterial infections in cirrhosis are common and associated with increased mortality, but little is known about fungal infections. The aim of this study, a sub-analysis of the Fungal Infection Risk Evaluation study, was to assess the incidence and implications of early invasive fungal disease (IFD) in patients with cirrhosis admitted to intensive care units (ICU). Clinical and laboratory parameters collected in the first 3 days of ICU stay for 782 patients with cirrhosis and/or portal hypertension were analysed and compared with those of 273 patients with very severe cardiovascular disease (CVD). The CVD patients had more co-morbidities and higher APACHE II scores. The overall incidence of IFD was similar in the two groups, but the incidence of IFD in ICU was higher in liver patients (1% versus 0.4%; p 0.025) as was fungal colonization (23.8% versus 13.9%; p 0.001). The ICU and in-hospital mortality, and length of stay were similar in the two groups. A higher proportion of liver patients received antifungal therapy (19.2% versus 7%; p <0.0005). There was no difference in mortality between colonized patients who received antifungal therapy and colonized patients who did not. The incidence of IFD in patients with cirrhosis in ICU is higher compared with another high-risk group, although it is still very low. This risk might be higher in patients with advanced liver disease admitted with acute-on-chronic liver failure, and this should be investigated further. Our data do not support prophylactic use of antifungal therapy in cirrhosis. Clinical Microbiology and Infection

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“…[1][2][3] Three critical factors that facilitate translocation of bacteria in patients with cirrhosis are: alterations in the intestinal microbiota, defective immune system and dysfunction of the intestinal epithelial barrier. .…”

Section: K Makhariamentioning

confidence: 99%

Intestinal permeabililty in portal hypertension: Still a dilemma

Makharia¹

2013

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Intestinal epithelial barrier function in liver cirrhosis: an extensive review of the literature

Cited by 109 publications

References 154 publications

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

Early invasive fungal infections and colonization in patients with cirrhosis admitted to the intensive care unit

Intestinal permeabililty in portal hypertension: Still a dilemma

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