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Targeted PGE2 inhibition enhances anti-viral immunity through induction of Type I interferon in macrophages (P6180)

2013· article· en· W3356316 on OpenAlexaff
Maziar Divangahi, François Coulombe, Joanna Jaworska, Mark Verway, Fanny Tzalepis, Amir Hossein Massoud, Joshua Gillard, Gary Wong, Gary Kobinger, Philippe Joubert, Zhou Xing, William S. Powell

Bibliographic record

VenueThe Journal of Immunology · 2013
Typearticle
Languageen
FieldMedicine
TopicInflammatory mediators and NSAID effects
Canadian institutionsMcMaster UniversityPublic Health Agency of CanadaMcGill UniversityCentre hospitalier universitaire de QuébecMcGill University Health Centre
Fundersnot available
KeywordsImmunityInterferonInnate immune systemImmune systemVirusBiologyInfluenza A virusViral replicationImmunologyProstaglandin E2 receptorMacrophageVirologyReceptorIn vitro

Abstract

fetched live from OpenAlex

Abstract The 1918 Spanish Influenza virus pandemic had a major impact on the rise in popularity of non-steroidal anti-inflammatory drugs (NSAIDs). Although these drugs are used extensively for the management of Influenza symptoms, their role in anti-viral immunity is poorly understood. NSAIDs act mainly by inhibiting cyclooxygenase enzymes involved in the synthesis of all prostaglandins, including PGE2. We now show that during Influenza infection, upregulated PGE2 inhibited macrophage type I interferon production and apoptosis via EP2 and EP4 receptors, thereby increasing virus replication. This inhibitory role of PGE2 was not limited to innate immunity since both antigen presentation and T cell mediated immunity were also suppressed. Inhibition of microsomal prostaglandin E-synthase 1 (mPGES-1), and thereby PGE2, in human Mϕ was protective against Flu infection. These data show that the mPGES-1/PGE2 pathway is specifically targeted by Influenza virus to evade host anti-viral immunity and propose that specific inhibition of PGE2 may serve as a new treatment for viral infection.

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 score0.002
Threshold uncertainty score0.006

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)0.0020.001

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 head0.012
GPT teacher head0.260
Teacher spread0.248 · 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
Published2013
Admission routes1
Has abstractyes

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