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Interleukin-35 inhibits angiogenesis through STAT1 signalling in rheumatoid synoviocytes
S. Wu1, Y. Li2, L. Yao3, Y. Li4, S. Jiang5, W. Gu6, H. Shen7, L. Xia8, J. Lu9
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang; Department of Immunology and Microbiology, Liaoning Vocational College of Medicine, Shenyang, China.
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Sports Medicine and Joint Surgery, 1st Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology and Immunology, the First Affiliated Hospital of China Medical Universit, Shenyangy; Department of Respiratory Medicine, Affiliated Center Hospital of Shenyang Medical College, Shenyang, China.
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
- Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China. lujingtan@163.com
CER10229
2018 Vol.36, N°2
PI 0223, PF 0227
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PMID: 28850026 [PubMed]
Received: 31/12/2016
Accepted : 26/06/2017
In Press: 28/08/2017
Published: 18/04/2018
Abstract
OBJECTIVES:
We studied the anti-angiogenic effect of interleukin-35 (IL-35) by investigating its effects on signal transmission through the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in fibroblast-like synoviocytes (FLS).
METHODS:
Using the collagen-induced arthritis (CIA) model of rheumatoid arthritis (RA), we derived and cultured FLS, stimulated FLS with IL-35 at different concentrations and examined the expression levels of mRNA and protein of both vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), endostatin, TNF-α, and IL-6 using reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting. We used Western blotting to study the effects of IL-35 on the function of the JAK-STAT pathway in FLS.
RESULTS:
IL-35 treatment inhibited the expression of VEGF, FGF-2, TNF-α and IL-6, and increased the expression of endostatin in FLS. Western blotting showed that IL-35 treatment of CIA-derived FLS resulted in signalling through STAT1, but not through STAT3 or STAT5.
CONCLUSIONS:
IL-35 signalling through STAT1 and inhibition of the expression of mediators of angiogenesis and inflammation in FLS provide a likely mechanism for anti-angiogenic effects seen in experimental models of RA. Our data suggest that IL-35 and its signalling pathway represent a therapeutic target for the treatment of RA and other angiogenesis-related diseases.