Interleukin 17 (IL-17) increases the expression of Toll-like receptor-2, 4, and 9 by increasing IL-1beta and IL-6 production in autoimmune arthritis.
OBJECTIVE
To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.


METHODS
On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1beta, TNF-alpha, and IL-6 was determined by real-time RT-PCR.


RESULTS
In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1beta, TNF-alpha and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1beta, and IL-6.


CONCLUSIONS
IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1beta and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1beta and IL-6 production are involved in the IL-17-induced aggravation of arthritis.
Lee
Jun-Hee
JH
Division of Rheumatology, Department of Internal Medicine, College of Medicine, Pusan National University, and Pusan National University Hospital Research Institutes,1-10, Ami-Dong, Seo-Gu, Busan, South Korea.
Cho
Mi-La
ML
Kim
Ju-In
JI
Moon
Young-Mee
YM
Oh
Hye-Jwa
HJ
Kim
Geun-Tae
GT
Ryu
Sun
S
Baek
Seung-Hoon
SH
Lee
Sun-Hee
SH
Kim
Ho-Youn
HY
Kim
Sung-Il
SI
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D007719:Knee Joint / Q000033:anatomy & histology / Q000276:immunology / Q000473:pathology; D051379:Mice; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha