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Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout

Overview of attention for article published in Arthritis Research & Therapy, November 2016
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Title
Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout
Published in
Arthritis Research & Therapy, November 2016
DOI 10.1186/s13075-016-1167-y
Pubmed ID
Authors

Lei Liu, Yu Xue, Yingfeng Zhu, Dandan Xuan, Xue Yang, Minrui Liang, Juan Wang, Xiaoxia Zhu, Jiong Zhang, Hejian Zou

Abstract

Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate immunity. Acute gout is a self-limiting inflammatory response to monosodium urate (MSU) crystals. In the current study, we assessed the preventive and therapeutic effect of recombinant human IL-37 (rhIL-37) in human and murine gout models. We investigated the expression of IL-37 in patients with active and inactive gouty arthritis and assessed the effect of rhIL-37 in human and murine gout models: a human monocyte cell line (THP-1) and human synovial cells (containing macrophage-like and fibroblast-like synoviocytes) exposed to MSU crystals, a peritoneal murine model of gout and a murine gouty arthritis model. After inhibition of Mer receptor tyrosine kinase (Mertk), levels of IL-1β, IL-8 and chemokine (C-C motif) ligand 2 (CCL-2) were detected by ELISA and expression of mammalian homologs of the drosophila Mad gene 3 (Smad), suppressor of cytokine signaling 3 (SOCS3), NACHT-LRR-PYD-containing protein 3 (NLRP3), and IL-8R of THP-1 were assessed by qPCR and western blot to explore the molecular mechanisms. Our studies strongly indicated that rhIL-37 played a potent immunosuppressive role in the pathogenesis of experimental gout models both in vitro and in vivo, by downregulating proinflammatory cytokines and chemokines, markedly reducing neutrophil and monocyte recruitment, and mitigating pathological joint inflammation. In our studies, rhIL-37 suppressed MSU-induced innate immune responses by enhancing expression of Smad3 and IL-1R8 to trigger multiple intracellular switches to block inflammation, including inhibition of NLRP3 and activation of SOCS3. Mertk signaling participated in rhIL-37 inhibitory pathways in gout models. By inhibition of Mertk, the anti-inflammatory effect of rhIL-37 was partly abrogated, and IL-1R8, Smad3 and S​OCS3 expression were suppressed, whereas NLRP3 expression was reactivated. Our studies reveal that IL-37 limits runaway inflammation initiated by MSU crystal-induced immune responses, partly in a Mertk-dependent fashion. Thus, rhIL-37 has both preventive and therapeutic effects in gouty arthritis.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 41 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 6 15%
Student > Postgraduate 5 12%
Student > Master 5 12%
Student > Ph. D. Student 4 10%
Student > Bachelor 3 7%
Other 10 24%
Unknown 8 20%
Readers by discipline Count As %
Medicine and Dentistry 14 34%
Immunology and Microbiology 5 12%
Pharmacology, Toxicology and Pharmaceutical Science 4 10%
Biochemistry, Genetics and Molecular Biology 4 10%
Agricultural and Biological Sciences 1 2%
Other 2 5%
Unknown 11 27%
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 28 November 2016.
All research outputs
#17,285,668
of 25,373,627 outputs
Outputs from Arthritis Research & Therapy
#2,536
of 3,381 outputs
Outputs of similar age
#260,054
of 415,795 outputs
Outputs of similar age from Arthritis Research & Therapy
#44
of 56 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% 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 16th percentile – i.e., 16% 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 415,795 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 28th percentile – i.e., 28% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 56 others from the same source and published within six weeks on either side of this one. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.