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PTP1B negatively regulates <i>Pseudomonas aeruginosa</i> killing by neutrophil through TLR4-STAT1-iNOS signaling

2019· article· en· W4313381305 on OpenAlexaff
Lei Yue, Hua Li, Ting Yang, Tong‐Jun Lin, Zhongping Xie

Bibliographic record

VenueThe Journal of Immunology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicProtein Tyrosine Phosphatases
Canadian institutionsDalhousie University
Fundersnot available
KeywordsPseudomonas aeruginosaTLR4Innate immune systemBiologyImmunologyImmune systemSTAT1Signal transductionMicrobiologyCell biologyInterferon

Abstract

fetched live from OpenAlex

Abstract Pseudomonas aeruginosa is a major opportunistic pathogen in immune-compromised individuals and chronic obstructive pulmonary diseases (COPD) patients. Mechanisms involved in immune responses to P. aeruginosa infection and bacterial clearance remain incompletely defined. Here we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a critical negative regulator in P. aeruginosa killing by neutrophil. PTP1B-deficient neutrophil display greatly enhanced bacterial killing capability and TLR4 transcription following P. aeruginosa infection. The negative regulation of PTP1B on the production of nitric oxide by neutrophil is blocked by TLR4 antagonist. Furthermore, the STAT1 activation in neutrophils following P. aeruginosa infection occurs in the downstream of TLR4, and PTP1B deficiency leads to enhanced TLR4 dependent STAT1 activation and iNOS expression by neutrophil. Interestingly, PTP1B deficiency mainly up-regulates the production of pro-inflammatory cytokines by neutrophil, including IL-6, IL-1β and TNFα, but only IL-6 is blocked by TLR4 antagonist. Further studies reveal that PTP1B and STAT1 are physically associated. These findings demonstrate a novel regulatory mechanism of the immune response to P. aeruginosa infection through PTP1B-STAT1 interaction. This novel PTP1B-STAT1-iNOS pathway may have broader implications in Toll-like receptor mediated innate immunity.

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 score0.005

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

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 head0.007
GPT teacher head0.221
Teacher spread0.214 · 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".

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Citations0
Published2019
Admission routes1
Has abstractyes

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