Endogenous IL-1 and Type II IL-1 Receptor Expression Modulate Anoikis in Intestinal Epithelial Cells

Waterhouse, Christopher C. M.; Joseph, Robbie R.; Stadnyk, Andrew W.

doi:10.1006/excr.2001.5303

Cited by 16 publications

(16 citation statements)

References 37 publications

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“…Furthermore, the increase did not result in a significantly greater number of cells surviving to 24 h post detachment. This outcome contrasts with our previous results and the results of others showing that stimulating NF-kB activity in detached cells is antiapoptotic (Chen et al, 2000;Waterhouse et al, 2001). This may be due to the magnitude of activation or the exogenous NF-kB triggers possibly activating other signalling pathways that complement the effect of NF-kB acting through the canonical pathway.…”

Section: Discussioncontrasting

confidence: 99%

“…Roughly 40% of detached IEC-18 survive to 24 h if the cells are prevented from reattaching (Waterhouse et al, 2001). In addition, we showed that immediately following detachment, IEC-18 express IL-1b and the IL-1 receptor type II (Waterhouse and Stadnyk, 1999), and Miller and McGee (2002) showed that IL-6 was upregulated by detachment, suggesting that IEC are programmed to trigger inflammation.…”

Section: Introductionmentioning

confidence: 81%

“…Others showed IL-8 expression due to detachment of bronchial epithelial cells (Shibata et al, 1996), implying that this may be a common feature of mucosal epithelial cells. We subsequently determined that IL-1 promotes survival of detached IEC-18 and thus the detached cells would seem to be expressing mediators that not only contribute to inflammation but also may affect apoptosis in vivo (Waterhouse et al, 2001). IL-1b, IL-6 and IL-8 expression are all regulated to some extent by the transcription factor NF-kB, but whether NF-kB becomes activated directly as a result of detachment has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Activation of NF-κB following detachment delays apoptosis in intestinal epithelial cells

et al. 2005

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

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Activation of NF-κB following detachment delays apoptosis in intestinal epithelial cells

et al. 2005

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“…Although high levels of IL-1␤ have been implicated in inflammatory diseases (3,8) including type 2 diabetes (9 -12), low levels have beneficial effects on pancreatic beta cell function, proliferation, and survival (13)(14)(15)(16), intestinal epithelial cell survival (17,18), and neuronal response to injury (19). As in many receptor-ligand systems, IL-1␤ signaling is complex, with multiple ligands interacting with membranebound and soluble forms of several receptors (20).…”

mentioning

confidence: 99%

Kinetic Approach to Pathway Attenuation Using XOMA 052, a Regulatory Therapeutic Antibody That Modulates Interleukin-1β Activity

Roell

Issafras

Bauer³

et al. 2010

Journal of Biological Chemistry

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Many therapeutic antibodies act as antagonists to competitively block cellular signaling pathways. We describe here an approach for the therapeutic use of monoclonal antibodies based on context-dependent attenuation to reduce pathologically high activity while allowing homeostatic signaling in biologically important pathways. Such attenuation is achieved by modulating the kinetics of a ligand binding to its various receptors and regulatory proteins rather than by complete blockade of signaling pathways. The anti-interleukin-1␤ (IL-1␤) antibody XOMA 052 is a potent inhibitor of IL-1␤ activity that reduces the affinity of IL-1␤ for its signaling receptor and co-receptor but not for its decoy and soluble inhibitory receptors. This mechanism shifts the effective dose response of the cytokine so that the potency of IL-1␤ bound by XOMA 052 is 20 -100-fold lower than that of IL-1␤ in the absence of antibody in a variety of in vitro cell-based assays. We propose that by decreasing potency of IL-1␤ while allowing binding to its clearance and inhibitory receptors, XOMA 052 treatment will attenuate IL-1␤ activity in concert with endogenous regulatory mechanisms. Furthermore, the ability to bind the decoy receptor may reduce the potential for accumulation of antibody⅐target complexes. Regulatory antibodies like XOMA 052, which selectively modulate signaling pathways, may represent a new mechanistic class of therapeutic antibodies.

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“…12 In detachment experiments, both cell-matrix and cell-cell contacts are disrupted, and aggregate formation can be enhanced under certain conditions, for example IL-1 stimulation. 13 In a study by Douma and colleagues, intestinal epithelial cells rendered anoikis resistant by TrkB also formed aggregates during anoikis. 8 Survival signalling in these aggregated cells may be complemented by cell-cell adhesion, such as E-cadherin or β 1 -integrins.…”

Section: Introductionmentioning

confidence: 97%

Prostaglandins and activation of AC/cAMP prevents anoikis in IEC-18

et al. 2005

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Recent data indicates that chronic inflammation of the intestine such as Crohn's or ulcerative colitis puts those individuals at heightened risk for colorectal adenocarcinoma. In this study, we examine the effect of the inflammatory mediator PGE(2) and associated signalling on detachment-induced cell death (anoikis) in intestinal epithelial cells. Treatment of detached IEC-18 with 0.01-0.05 microM PGE(2) increased cell viability as well as induced aggregation. As EP4 prostaglandin receptors on IEC are coupled to adenylate cyclase, we next treated cells with agents that promote cAMP signalling (Forskolin, dbcAMP, and etazolate), all of which promoted IEC aggregation as well as survival. We next treated detached IECs with specific inhibitors of adenylate cyclase or PKA, which accelerated anoikis. To explore the mechanism of cell-cell adhesion, we next treated detached IECs with an anti-E-cadherin blocking antibody which dispersed aggregates induced by dbcAMP, and an adenovirus expressing a dominant negative E-cadherin (EcadDeltaEC) prevented aggregate formation. Interestingly EcadDeltaEC prevented aggregation of IEC induced by dbcAMP but did not significantly reduce viability. This suggests that cAMP signalling is important in both aggregate formation and promoting viability but these are distinct events. Taken together, these data support a mechanism whereby elevated PGE(2) levels characteristic of colitis prevent anoikis by activating an AC-, cAMP-, and PKA-dependent signalling pathway. The delay of apoptosis by PGE(2) may be one mechanism by which inflammation may contribute to carcinogenesis.

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Endogenous IL-1 and Type II IL-1 Receptor Expression Modulate Anoikis in Intestinal Epithelial Cells

Cited by 16 publications

References 37 publications

Activation of NF-κB following detachment delays apoptosis in intestinal epithelial cells

Activation of NF-κB following detachment delays apoptosis in intestinal epithelial cells

Kinetic Approach to Pathway Attenuation Using XOMA 052, a Regulatory Therapeutic Antibody That Modulates Interleukin-1β Activity

Prostaglandins and activation of AC/cAMP prevents anoikis in IEC-18

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