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T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model

Overview of attention for article published in Journal of Intensive Care, November 2015
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Title
T-5224, a selective inhibitor of c-Fos/activator protein-1, improves survival by inhibiting serum high mobility group box-1 in lethal lipopolysaccharide-induced acute kidney injury model
Published in
Journal of Intensive Care, November 2015
DOI 10.1186/s40560-015-0115-2
Pubmed ID
Authors

Mari Ishida, Masaaki Ueki, Jun Morishita, Masaki Ueno, Shunichi Shiozawa, Nobuhiro Maekawa

Abstract

Sepsis is a potentially fatal syndrome mediated by an early [e.g., tumor necrosis factor-alpha (TNF-α)] and late [high mobility group box-1 (HMGB-1)] proinflammatory cytokine response to infection. Sepsis-induced acute kidney injury (AKI) is associated with a high mortality. C-Fos/activator protein-1 (AP-1) controls the transactivation of proinflammatory cytokines via AP-1 binding in the promoter region. T-5224 is a de novo small molecule inhibitor of c-Fos/AP-1 that controls gene expression of multiple proinflammatory cytokines. We investigated whether T-5224, a selective inhibitor of c-Fos/AP-1, improves survival in lethal lipopolysaccharide (LPS)-induced AKI by inhibiting early (TNF-α) and late (HMGB-1) proinflammatory cytokine response. Mice were divided into four groups (control, LPS, LPS + T-5224, and T-5224 only). Control mice were administered polyvinylpyrrolidone (PVP) solution orally, immediately after intraperitoneal (i.p.) saline injection. LPS mice were administered PVP solution orally immediately after i.p. LPS (10 mg/kg) injection. LPS + T-5224 mice were administered T-5224 orally (300 mg/kg) immediately after i.p. LPS injection. T-5224 mice were administered T-5224 orally (300 mg/kg) after i.p. saline injection. Serum concentrations of TNF-α, HMBG-1, and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay (ELISA). Serum blood urea nitrogen (BUN) and creatinine concentrations were commercially analyzed. Finally, histological examination was performed on the kidney. Treatment with T-5224 decreased serum TNF-α and HMGB-1 levels and increased survival after LPS injection. Furthermore, T-5224 treatment decreased serum BUN and creatinine concentrations but increased serum IL-10 concentration. LPS-induced pathological changes in kidney were attenuated by T-5224 treatment. These results suggest that T-5224, a selective inhibitor of c-Fos/AP-1, inhibits expression of early and late proinflammatory cytokines, protecting mice from LPS-induced lethality. T-5224 is a potential approach for decreasing lethality in sepsis-induced AKI.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 43%
Student > Ph. D. Student 4 29%
Professor 1 7%
Other 1 7%
Student > Postgraduate 1 7%
Other 0 0%
Unknown 1 7%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 36%
Immunology and Microbiology 3 21%
Neuroscience 2 14%
Medicine and Dentistry 1 7%
Agricultural and Biological Sciences 1 7%
Other 0 0%
Unknown 2 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 November 2015.
All research outputs
#4,872,322
of 6,585,900 outputs
Outputs from Journal of Intensive Care
#111
of 136 outputs
Outputs of similar age
#168,725
of 248,156 outputs
Outputs of similar age from Journal of Intensive Care
#14
of 18 outputs
Altmetric has tracked 6,585,900 research outputs across all sources so far. This one is in the 14th percentile – i.e., 14% of other outputs scored the same or lower than it.
So far Altmetric has tracked 136 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one is in the 6th percentile – i.e., 6% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 248,156 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 20th percentile – i.e., 20% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 18 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.