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Interleukin‐1 receptor activates Rho kinase to disrupt epithelial tight junctions during <i>Helicobacter pylori</i> infection

2009· article· en· W2289082306 on OpenAlexafffund
Tamia K. Lapointe, Pamela M. J. O’Connor, Daniel Ménard, André G. Buret

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldMedicine
TopicHelicobacter pylori-related gastroenterology studies
Canadian institutionsUniversité de SherbrookeUniversity of Calgary
FundersCanadian Institutes of Health Research
KeywordsTight junctionProinflammatory cytokineBarrier functionBlocking antibodyPhosphorylationHelicobacter pyloriReceptorKinaseChemistryCell biologyAntibodyBiologyImmunologyInflammation

Abstract

fetched live from OpenAlex

The ability of H. pylori (Hp) to modulate tight junction (TJ) permeability may contribute to the development of gastric ulcers and adenocarcinomas. Rho kinase (ROCK) and interleukin (IL)‐1β are known to modulate tight junction (TJ) function. While Hp induces IL‐1β expression, the role of this proinflammatory cytokine and ROCK in Hp‐mediated TJ disruption remains elusive. AIM This study investigated the role of ROCK and IL‐1β in Hp‐mediated TJ disruption in human gastric epithelial (HGE‐20) cells. RESULTS HGE‐20 monolayers challenged with either Hp or IL‐1β showed an increase in ROCK activity 6 h post infection, which coincided with redistribution and loss of claudin‐4. Inhibition of ROCK prior to bacterial challenge prevented these effects. Hp infection also induced IL‐1 receptor (IL‐1R) phosphorylation. Nevertheless, no increase in IL‐1β could be detected in supernatants of infected monolayers and treatment with co‐culture conditioned media failed to induce IL‐1R phosphorylation. While an IL‐1β neutralizing antibody did not prevent Hp‐induced IL‐1R activation, the use of an IL‐1R blocking antibody prior to infection prevented Hp‐mediated ROCK activation and claudin‐4 loss. CONCLUSION These findings suggest that the mechanism by which Hp disrupts gastric epithelial barrier structure involves IL‐1R ‐dependent activation of ROCK, which mediates claudin‐4 disruption. This work was funded by CIHR.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.257
Teacher spread0.243 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2009
Admission routes2
Has abstractyes

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