IL-17 induces the production of IL-16 in rheumatoid arthritis.
10.3858/emm.2008.40.2.237
- Author:
Mi La CHO
1
;
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
Author Information
1. Division of Rheumatology, Department of Internal Medicine, The Rheumatism Research Center, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea. rapark@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
interleukin-16;
interleukin-17;
rheumatoid arthritis;
synovial membrane;
Toll-like receptors
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(2):237-245
- CountryRepublic of Korea
- Language:English
-
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.
