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KMID : 0620920120440070424
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Experimental & Molecular Medicine
2012 Volume.44 No. 7 p.424 ~ p.431
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Obesity aggravates the joint inflammation in a collagen-induced arthritis model through deviation to Th17 differentiation
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Jhun Joo-Yeon
Yoon Bo-Young
Park Mi-Kyung
Oh Hye-Joa
Byun Jae-Kyeong
Lee Seon-Young
Min Jun-Ki
Park Sung-Hwan
Kim Ho-Youn
Cho Mi-La
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Abstract
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White fat cells secrete adipokines that induce inflammation and obesity has been reported to be characterized by high serum levels of inflammatory cytokines such as IL-6 and TNF-α. Rheumatoid arthritis (RA) is a prototype of inflammatory arthritis, but the relationship between RA and obesity is controversial. We made an obese inflammatory arthritis model: obese collagen-induced arthritis (CIA). C57BL/6 mice were fed a 60-kcal high fat diet (HFD) from the age of 4 weeks and they were immunized twice with type II collagen (CII). After immunization, the obese CIA mice showed higher arthritis index scores and histology scores and a more increased incidence of developing arthritis than did the lean CIA mice. After treatment with CII, mixed lymphocyte reaction also showed CII-specific response more intensely in the obese CIA mice than lean CIA. The anti-CII IgG and anti-CII IgG2a levels in the sera of the obese CIA mice were higher than those of the lean CIA mice. The number of Th17 cells was higher and the IL-17 mRNA expression of the splenocytes in the obese CIA mice was higher than that of the lean CIA mice. Obese CIA mice also showed high IL-17 expression on synovium in immunohistochemistry. Although obesity may not play a pathogenic role in initiating arthritis, it could play an important role in amplifying the inflammation of arthritis through the Th1/Th17 response. The obese CIA murine model will be an important tool when we investigate the effect of several therapeutic target molecules to treat RA.
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KEYWORD
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arthritis, experimental, inflammation, mice, obesity, Th17 cells
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