IL-17 induces the production of IL-16 in rheumatoid arthritis.
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.
Cho
Mi-La
ML
Division of Rheumatology, Department of Internal Medicine, The Rheumatism Research Center, The Catholic University of Korea College of Medicine, Seoul 137-701, Korea.
Jung
Young Ok
YO
Kim
Kyoung-Woon
KW
Park
Mi-Kyung
MK
Oh
Hye-Joa
HJ
Ju
Ji-Hyeon
JH
Cho
Young-Gyu
YG
Min
Jun-Ki
JK
Kim
Sung-Il
SI
Park
Sung-Hwan
SH
Kim
Ho-Youn
HY
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D019410:Interleukin-16 / Q000096:biosynthesis* / Q000235:genetics; D020381:Interleukin-17 / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051195:Toll-Like Receptor 2 / Q000378:metabolism
D017931:DNA Primers; D019410:Interleukin-16; D020381:Interleukin-17; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2