Effective Treatment of Gut Barrier Dysfunction Using an Antioxidant, a PAF Inhibitor, and Monoclonal Antibodies against the Adhesion Molecule PECAM-1

Sun, Zhengwu; Olanders, Knut; Lasson, Åke; Dib, Marwan; Annborn, M; Andersson, Klara; Wang, Xiangdong; Andersson, Roland

doi:10.1006/jsre.2001.6342

Cited by 39 publications

(19 citation statements)

References 25 publications

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“…30 Antithrombin-III itself could play a role in I/R injury, since its exogenous administration has been shown to reduce intestinal I/R injury. 31 Ketamine pretreatment reduced the depletion of the serum concentrations of ATIII after I/R.…”

Section: Discussionmentioning

confidence: 99%

Ketamine reduces intestinal injury and inflammatory cell infiltration after ischemia/reperfusion in rats

et al. 2010

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Section: Discussionmentioning

confidence: 99%

Ketamine reduces intestinal injury and inflammatory cell infiltration after ischemia/reperfusion in rats

et al. 2010

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“…Recent studies from our laboratory and others have shown (8,33,34) that IL-1␤ causes an increase in intestinal TJ permeability. The IL-1␤-induced increase in intestinal TJ permeability has been postulated to play an important role in promoting intestinal inflammation by allowing increased paracellular permeation of luminal Ags (8).…”

Section: T He Defective Intestinal Epithelial Tight Junction (Tj)mentioning

confidence: 91%

Mechanism of IL-1β-Induced Increase in Intestinal Epithelial Tight Junction Permeability

Al–Sadi

Dokładny

et al. 2008

The Journal of Immunology

361

295

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The IL-1β-induced increase in intestinal epithelial tight junction (TJ) permeability has been postulated to be an important mechanism contributing to intestinal inflammation of Crohn’s disease and other inflammatory conditions of the gut. The intracellular and molecular mechanisms that mediate the IL-1β-induced increase in intestinal TJ permeability remain unclear. The purpose of this study was to elucidate the mechanisms that mediate the IL-1β-induced increase in intestinal TJ permeability. Specifically, the role of myosin L chain kinase (MLCK) was investigated. IL-1β caused a progressive increase in MLCK protein expression. The time course of IL-1β-induced increase in MLCK level correlated linearly with increase in Caco-2 TJ permeability. Inhibition of the IL-1β-induced increase in MLCK protein expression prevented the increase in Caco-2 TJ permeability. Inhibition of the IL-1β-induced increase in MLCK activity also prevented the increase in Caco-2 TJ permeability. Additionally, knock-down of MLCK protein expression by small interference RNA prevented the IL-1β-induced increase in Caco-2 TJ permeability. The IL-1β-induced increase in MLCK protein expression was preceded by an increase in MLCK mRNA expression. The IL-1β-induced increase in MLCK mRNA transcription and subsequent increase in MLCK protein expression and Caco-2 TJ permeability was mediated by activation of NF-κB. In conclusion, our data indicate that the IL-1β increase in Caco-2 TJ permeability was mediated by an increase in MLCK expression and activity. Our findings also indicate that the IL-1β-induced increase in MLCK protein expression and Caco-2 TJ permeability was mediated by an NF-κB-dependent increase in MLCK gene transcription.

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“…A considerable number of studies have demonstrated a direct linear correlation between cold ischemic time, ischemia-reperfusion injury, and adaptive immune reactions during rejection, such as graft coronary artery disease (16). There is clear evidence that PECAM-1 contributes to ischemia-reperfusion injury and that functional blockade of this molecule significantly attenuates manifestation of tissue damage and organ dysfunction (4,17). Because it is thought that ischemia-reperfusion injury influences manifestation of chronic rejection, it may be assumed that inhibition of PECAM-1 may also reduce later manifestation of graft coronary artery vasculopathy.…”

Section: Discussionmentioning

confidence: 99%

Role of PECAM-1 in Acute Rejection of Fully Major Histocompatibility Complex Class II-Mismatched Cardiac Allografts in Mice

et al. 2007

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The aim of this study was to determine the role of platelet-endothelial cell adhesion molecule (PECAM) in acute rejection of vascularized whole organ allografts in vivo. Hearts were transplanted between BALB/c, PECAM-1(-/-), or C57BL/6 wild-type mice. Grafts were harvested on the day of rejection or after 120 days and were analyzed histologically. BALB/c allografts survived significantly longer in PECAM-1(-/-) recipients compared to wild-type controls (8.3+/-0.4 vs. 6.4+/-0.8 days; P<0.05). Survival of PECAM-1(-/-) allografts in BALB/c recipients did not differ from that of wild-type-derived transplants (12.2+/-3.0 vs. 9.3+/-0.7; P>0.05). In all allografts, histology showed massive monomorphonuclear leukocyte infiltration, indicating parenchymal rejection. Immunohistochemistry confirmed in all transplants a preserved donor endothelial phenotype. Our data indicate a subtle role of nonendothelial PECAM-1 in acute allograft rejection. Although deletion of PECAM-1 could not prevent rejection, it should be further evaluated as a therapeutic target in more complex settings with concomitant immunosuppression or during chronic rejection.

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Effective Treatment of Gut Barrier Dysfunction Using an Antioxidant, a PAF Inhibitor, and Monoclonal Antibodies against the Adhesion Molecule PECAM-1

Cited by 39 publications

References 25 publications

Ketamine reduces intestinal injury and inflammatory cell infiltration after ischemia/reperfusion in rats

Ketamine reduces intestinal injury and inflammatory cell infiltration after ischemia/reperfusion in rats

Mechanism of IL-1β-Induced Increase in Intestinal Epithelial Tight Junction Permeability

Role of PECAM-1 in Acute Rejection of Fully Major Histocompatibility Complex Class II-Mismatched Cardiac Allografts in Mice

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