RESEARCH - IL-17 increases the expression of TLR-2, 4 and 9 by increasing production of IL-1 and IL-6

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J Rheumatol. 2009 Feb 17. [Epub ahead of print]

Interleukin 17 (IL-17) Increases the Expression of Toll-like

Receptor-2, 4, and 9 by Increasing IL-1{beta} and IL-6 Production in

Autoimmune Arthritis.

Lee JH, Cho ML, Kim JI, Moon YM, Oh HJ, Kim GT, Ryu S, Baek SH, Lee

SH, Kim HY, Kim SI.

From the Department of Internal Medicine, College of Medicine, Pusan

National University, Busan; Pusan National University Hospital

Research Institutes; and The Rheumatism Research Center, Catholic

University of Korea, Seoul, South Korea.

OBJECTIVE: To examine the effect of interleukin 17 (IL-17) onthe

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-1ss, 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-1ss,TNF-alpha, and

IL-6 was determined by realtime 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-1ss,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-1ss, and IL-6.

CONCLUSION: IL-17 aggravates joint inflammation and destruction, and

increases the synovial expression of TLR-2, 4, and 9 by increasing

IL-1ss and IL-6. These results imply that the IL-17-induced increase

in expression of TLR-2, 4, and 9, and IL-1ss and IL-6 production are

involved in the IL-17- induced aggravation of arthritis.

PMID: 19228664

http://www.ncbi.nlm.nih.gov/pubmed/19228664

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