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Interleukin-35 inhibits angiogenesis through STAT1 signalling in rheumatoid synoviocytes

1, 2, 3, 4, 5, 6, 7, 8, 9

  1. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang; Department of Immunology and Microbiology, Liaoning Vocational College of Medicine, Shenyang, China.
  2. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
  3. Department of Sports Medicine and Joint Surgery, 1st Affiliated Hospital of China Medical University, Shenyang, China.
  4. 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.
  5. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
  6. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
  7. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
  8. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China.
  9. Department of Rheumatology, 1st Affiliated Hospital of China Medical University, Shenyang, China. lujingtan@163.com

CER10229 Submission on line
Full Papers

Rheumatology Article

 

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.

PMID: 28850026 [PubMed]

Received: 31/12/2016 - Accepted : 26/06/2017 - In Press: 28/08/2017