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Complementary action of granulocyte macrophage colony-stimulating factor and interleukin-17A induces interleukin-23, receptor activator of nuclear factor-κB ligand, and matrix metalloproteinases and…

Overview of attention for article published in Arthritis Research & Therapy, June 2015
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Title
Complementary action of granulocyte macrophage colony-stimulating factor and interleukin-17A induces interleukin-23, receptor activator of nuclear factor-κB ligand, and matrix metalloproteinases and drives bone and cartilage pathology in experimental arthritis: rationale for combination therapy in rheumatoid arthritis
Published in
Arthritis Research & Therapy, June 2015
DOI 10.1186/s13075-015-0683-5
Pubmed ID
Authors

Annemarie E. M. van Nieuwenhuijze, Fons A. van de Loo, Birgitte Walgreen, Miranda Bennink, Monique Helsen, Liduine van den Bersselaar, Ian P. Wicks, Wim B. van den Berg, Marije I. Koenders

Abstract

T helper 17 (Th17) cells and interleukin (IL)-17 play important roles in the pathogenesis of human and murine arthritis. Although there is a clear link between IL-17 and granulocyte-macrophage stimulating-factor (GM-CSF) in the inflammatory cascade, details about their interaction in arthritic synovial joints are unclear. In view of the introduction of GM-CSF- and IL-17-inhibitors to the clinic, we studied how IL-17 and GM-CSF orchestrate the local production of inflammatory mediators during experimental arthritis. To allow detection of additive, complementary or synergistic effects of IL-17 and GM-CSF, we used two opposing experimental approaches: treatment of arthritic mice with neutralising antibodies to IL-17 and GM-CSF, and local overexpression of these cytokines in naïve synovial joints. Mice were treated for two weeks with antibodies against IL-17 and/or GM-CSF after onset of collagen-induced arthritis (CIA). Naïve mice were injected intra-articularly with adenoviral vectors for IL-17 and/or GM-CSF, resulting in local overexpression. Joint inflammation was monitored by macroscopic scoring, X-ray and histology. Joint washouts, synovial cell- and lymph node cultures were analysed for cytokines, chemokines and inflammatory mediators by Luminex analysis, flow cytometry and quantitative polymerase chain reaction (QPCR). Combined therapeutic anti-IL-17 and anti-GM-CSF ameliorated arthritis progression, and joint damage was dramatically reduced compared to treatment with anti-IL-17 or anti-GM-CSF alone. Anti-IL-17 specifically reduced synovial IL-23 transcription, whereas anti-GM-CSF reduced transcription of matrix metalloproteinases (MMPs) and receptor activator of nuclear factor (NF)-κB ligand (RANKL). Overexpression of IL-17 or GM-CSF in naive knee joints elicited extensive inflammatory infiltrate, cartilage damage and bone destruction. Combined overexpression revealed additive and synergistic effects on the production of MMPs, RANKL and IL-23 in the synovium, and led to complete destruction of the joint structure within 7 days. IL-17 and GM-CSF differentially mediate the inflammatory process in arthritic joints, and show complementary and local additive effects. Combined blockade in arthritic mice reduced joint damage not only by direct inhibition of IL-17 and GM-CSF, but also by indirect inhibition of IL-23 and RANKL. Our results provide a rationale for combination therapy in auto-inflammatory conditions, especially for patients that do not fully respond to inhibition of the separate cytokines.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 15%
Student > Bachelor 4 10%
Researcher 3 8%
Student > Doctoral Student 3 8%
Other 2 5%
Other 8 21%
Unknown 13 33%
Readers by discipline Count As %
Medicine and Dentistry 8 21%
Agricultural and Biological Sciences 5 13%
Biochemistry, Genetics and Molecular Biology 4 10%
Nursing and Health Professions 3 8%
Immunology and Microbiology 2 5%
Other 5 13%
Unknown 12 31%
Attention Score in Context

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 26 March 2016.
All research outputs
#22,759,452
of 25,373,627 outputs
Outputs from Arthritis Research & Therapy
#3,132
of 3,381 outputs
Outputs of similar age
#236,664
of 277,757 outputs
Outputs of similar age from Arthritis Research & Therapy
#58
of 64 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 1st percentile – i.e., 1% 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 277,757 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 64 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.