Dataset Information

Shigella dysenteriae infection activates proinflammatory response through ?-catenin/NF-?B signaling pathway.

ABSTRACT: Shigella dysenteriae (S.dysenteriae) the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of ?-catenin and NF-?B regulates proinflammatory cytokines TNF-? and IL-8 by modulating GSK-3? activity during S.dysenteriae infection in rat ileal loop model. Here we demonstrated that S.dysenteriae infection stimulate ?-catenin degradation which in turn decreased the association between NF-?B and ?-catenin. Also, we showed that S.dysenteriae infection increased GSK-3? kinase activity which in turn phosphorylates ?-catenin for its degradation by ubiquitination and upregulates IL-8 through NF-?B activation thereby leading to inflammation. Thus these findings revealed the role of ?-catenin/ NF-?B and GSK-3? in modulating the inflammatory response during bacterial infection and also showed that ?-catenin acts as a critical regulator of inflammation.

SUBMITTER: Gopal A

PROVIDER: S-EPMC5400225 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Shigella dysenteriae infection activates proinflammatory response through β-catenin/NF-κB signaling pathway.

Gopal Ashidha A Chidambaram Iyer Soumya IS Devaraj Niranjali N Devaraj Halagowder H

PloS one 20170421 4

Shigella dysenteriae (S.dysenteriae) the causative agent of bacillary dysentery invades the human colonic epithelium resulting in severe intestinal inflammatory response and epithelial destruction. However, the mechanism by which S.dysenteriae infection regulates proinflammatory cytokines during intestinal inflammation is still obscure. In this study, we evaluated whether the interaction of β-catenin and NF-κB regulates proinflammatory cytokines TNF-α and IL-8 by modulating GSK-3β activity durin ...[more]

PMID: 28430783

Similar Datasets

Project description:The nuclear factor kappa B (NF-κB) is a potent transcription factor, activation of which typically results in robust proinflammatory signaling and triggering of fast negative feedback modulators to avoid excessive inflammatory responses. Here, we report that infection of epithelial cells, including primary porcine respiratory epithelial cells, with the porcine alphaherpesvirus pseudorabies virus (PRV) results in the gradual and persistent activation of NF-κB, illustrated by proteasome-dependent degradation of the inhibitory NF-κB regulator IκB and nuclear translocation and phosphorylation of the NF-κB subunit p65. PRV-induced persistent activation of NF-κB does not result in expression of negative feedback loop genes, like the gene for IκBα or A20, and does not trigger expression of prototypical proinflammatory genes, like the gene for tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6). In addition, PRV infection inhibits TNF-α-induced canonical NF-κB activation. Hence, PRV infection triggers persistent NF-κB activation in an unorthodox way and dramatically modulates the NF-κB signaling axis, preventing typical proinflammatory gene expression and the responsiveness of cells to canonical NF-κB signaling, which may aid the virus in modulating early proinflammatory responses in the infected host.IMPORTANCE The NF-κB transcription factor is activated via different key inflammatory pathways and typically results in the fast expression of several proinflammatory genes as well as negative feedback loop genes to prevent excessive inflammation. In the current report, we describe that infection of cells with the porcine alphaherpesvirus pseudorabies virus (PRV) triggers a gradual and persistent aberrant activation of NF-κB, which does not result in expression of hallmark proinflammatory or negative feedback loop genes. In addition, although PRV-induced NF-κB activation shares some mechanistic features with canonical NF-κB activation, it also shows remarkable differences; e.g., it is largely independent of the canonical IκB kinase (IKK) and even renders infected cells resistant to canonical NF-κB activation by the inflammatory cytokine TNF-α. Aberrant PRV-induced NF-κB activation may therefore paradoxically serve as a viral immune evasion strategy and may represent an important tool to unravel currently unknown mechanisms and consequences of NF-κB activation.

Dataset Information

Shigella dysenteriae infection activates proinflammatory response through ?-catenin/NF-?B signaling pathway.

Publications

Shigella dysenteriae infection activates proinflammatory response through β-catenin/NF-κB signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets