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p53 predominantly regulates IL-6 production and suppresses synovial inflammation in fibroblast-like synoviocytes and adjuvant-induced arthritis

Overview of attention for article published in Arthritis Research & Therapy, November 2016
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34 Mendeley
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Title
p53 predominantly regulates IL-6 production and suppresses synovial inflammation in fibroblast-like synoviocytes and adjuvant-induced arthritis
Published in
Arthritis Research & Therapy, November 2016
DOI 10.1186/s13075-016-1161-4
Pubmed ID
Authors

Ting Zhang, Huihua Li, Juan Shi, Sha Li, Muyuan Li, Lei Zhang, Leting Zheng, Dexian Zheng, Fulin Tang, Xuan Zhang, Fengchun Zhang, Xin You

Abstract

Dominant-negative somatic mutations of p53 has been identified in the synovium of patients with rheumatoid arthritis (RA), in which interleukin (IL)-6 has been established as a pivotal inflammatory cytokine. The aim of this study was to clarify the significance of p53 in the longstanding inflammation in RA by modulating IL-6. We established adjuvant-induced arthritis (AIA) in Lewis rats and treated them with p53 activator, and then analyzed the histopathology of the synovium and IL-6 expression. Human fibroblast-like synoviocytes (FLS) were cultured and transfected with p53-siRNA or transduced with adenovirus (Ad)-p53, and then assessed with MTT, TUNEL staining, and luciferase assay. IL-1β, tumor necrosis factor (TNF)-α and IL-17 were used to stimulate FLS, and subsequent IL-6 expression as well as relevant signal pathways were explored. p53 significantly reduced synovitis as well as the IL-6 level in the AIA rats. It controlled cell cycle arrest and proliferation, but not apoptosis. Proinflammatory cytokines inhibited p53 expression in FLS, while p53 significantly suppressed the production of IL-6. Furthermore, IL-6 expression in p53-deficient FLS was profoundly reduced by NF-kappaB, p38, JNK, and ERK inhibitors. Our findings reveal a novel function of p53 in controlling inflammatory responses and suggest that p53 abnormalities in RA could sustain and accelerate synovial inflammation mainly through IL-6. p53 may be a key modulator of IL-6 in the synovium and plays a pivotal role in suppressing inflammation by interaction with the signal pathways in RA-FLS. Interfering with the p53 pathway could therefore be an effective strategy to treat RA.

Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 26%
Researcher 4 12%
Student > Postgraduate 3 9%
Other 3 9%
Student > Ph. D. Student 3 9%
Other 3 9%
Unknown 9 26%
Readers by discipline Count As %
Medicine and Dentistry 7 21%
Agricultural and Biological Sciences 6 18%
Immunology and Microbiology 4 12%
Biochemistry, Genetics and Molecular Biology 3 9%
Pharmacology, Toxicology and Pharmaceutical Science 2 6%
Other 2 6%
Unknown 10 29%

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 14 February 2017.
All research outputs
#7,238,222
of 11,622,318 outputs
Outputs from Arthritis Research & Therapy
#1,152
of 1,602 outputs
Outputs of similar age
#152,016
of 259,198 outputs
Outputs of similar age from Arthritis Research & Therapy
#9
of 20 outputs
Altmetric has tracked 11,622,318 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,602 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 22nd percentile – i.e., 22% 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 259,198 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 20 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.