Interleukin-33 promotes proliferation and inhibits apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis.

Abstract

OBJECTIVES:

The aim of our study was to determine the effect of interleukin (IL)-33 on the proliferation, apoptosis, and secretion of inflammatory cytokines by fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) and to investigate the underlying mechanisms.

METHODS:

Cultured RA FLSs and osteoarthritis (OA) FLSs were cocultured with different concentrations of IL-33. TUNEL assay and flow cytometry were used to detect apoptosis. Western blotting and Real-time (RT)-PCR were used to detect the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), while the Cell Counting Kit-8 was used to determine cell proliferation in each cocultured group. Enzyme-linked immunosorbent assay was used to detect the expression levels of tumour necrosis factor (TNF)-α and IL-6 in the supernatant from each cell culture. Western blot analysis was used to determine the phosphorylated expression levels of the nuclear factor-kappa light chain enhancer of the activated B cells (NF-κB) pathway in each group.

RESULTS:

IL-33 inhibited RA FLS apoptosis, promoted FLS proliferation, increased Bcl-2 protein expression levels, and decreased Bax protein expression levels. It also increased the expression levels of inflammatory cytokines TNF-α and IL-6 and increased the expression levels of P-NF-κ B in FLSs.

CONCLUSIONS:

IL-33 inhibited apoptosis and promoted proliferation of FLSs; in addition, IL-33 increased the serum levels of inflammatory cytokines. The effect of IL-33 on RA FLSs was likely mediated via the NF-κB pathway.

• Authors: Suqin Wu, Yue Jiang, Ying Teng, Xiaoda Liu, Linan Zhou, Wenhui Li
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2021 Jul-Aug Vol. 39 Issue 4 Pg. 844-851 ISSN: 0392-856X [Print] Italy
• PMID: 33124566 (Publication Type: Journal Article)

Chemical References

• Interleukin-33
• NF-kappa B

Topics

• Apoptosis
• Arthritis, Rheumatoid (drug therapy)
• Cell Proliferation
• Cells, Cultured
• Fibroblasts
• Humans
• Interleukin-33
• NF-kappa B
• Synoviocytes