IL-17 induces the production of IL-16 in rheumatoid arthritis.

Abstract

The purpose of this study was to investigate the expression of IL-16 in the rheumatoid synovium and the role of inflammatory cytokines and Toll-like receptor (TLR) ligands in IL-16 production by fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients. Immunohistochemical staining was performed with a monoclonal antibody to IL-16 in synovial tissues from patients with RA and likewise in patients with osteoarthritis (OA). FLS were isolated from RA synovial tissues and stimulated with IL-15, IL-1beta, IFN-gamma, and IL-17. The IL-16 mRNA level was assessed by semiquantitative RT-PCR and real time (RT) PCR and a comparison was made between IL-16 mRNA levels produced by RA-FLS and OA-FLS. Production of IL-16 was identified by a western blot assay, and IL-16 production after stimulation by specific ligands of TLR2 and TLR4 was assessed by RT-PCR. While immunohistochemical staining demonstrated strong expression of IL-16 mRNA in synovial tissues from patients with RA, similar findings were not present in the OA group. Moreover, mRNA expression of IL-16 by RA-FLS increased after treatment with IL-17 but not with IL-15, IL-1beta, and IFN-gamma. Specifically, IL-17 increased IL-16 mRNA level by RA-FLS and peripheral blood mononuclear cells in a dose-dependent manner. However, IL-17 did not stimulate IL-16 production in OA-FLS. Peptidoglycan, a selective TLR2 ligand, also increased production of IL-16 by RA-FLS dose- dependently, whereas LPS, a selective TLR4 ligand, had no such stimulatory effect. The results from our data demonstrate that IL-17 and TLR2 ligands stimulate the production of IL-16 by RA-FLS.

• Authors: Mi-La Cho, Young Ok Jung, Kyoung-Woon Kim, Mi-Kyung Park, Hye-Joa Oh, Ji-Hyeon Ju, Young-Gyu Cho, Jun-Ki Min, Sung-Il Kim, Sung-Hwan Park, Ho-Youn Kim
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 40 Issue 2 Pg. 237-45 (Apr 30 2008) ISSN: 1226-3613 [Print] United States
• PMID: 18446062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Interleukin-16
• Interleukin-17
• RNA, Messenger
• Toll-Like Receptor 2

Topics

• Arthritis, Rheumatoid (metabolism)
• Base Sequence
• Blotting, Western
• DNA Primers
• Humans
• Immunohistochemistry
• Interleukin-16 (biosynthesis, genetics)
• Interleukin-17 (physiology)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Toll-Like Receptor 2 (metabolism)