Obesity aggravates the joint inflammation in a collagen-induced arthritis model through deviation to Th17 differentiation.
- Author:
Joo Yeon JHUN
1
;
Bo Young YOON
;
Mi Kyung PARK
;
Hye Joa OH
;
Jae Kyeong BYUN
;
Seon Young LEE
;
Jun Ki MIN
;
Sung Hwan PARK
;
Ho Youn KIM
;
Mi La CHO
Author Information
1. The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul 137-040, Korea. iammila@catholic.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
arthritis, experimental;
inflammation;
mice;
obesity;
Th17 cells
- MeSH:
Adipokines/immunology/metabolism;
Animals;
*Arthritis, Experimental/genetics/immunology/pathology;
Cell Differentiation/genetics/immunology;
*Collagen Type II/administration & dosage/immunology;
Disease Models, Animal;
Gene Expression;
Humans;
Inflammation/chemically induced/*immunology;
Interleukin-17/metabolism;
Interleukin-6/blood;
Joints/immunology/pathology;
Mice;
Mice, Inbred C57BL;
*Obesity/genetics/immunology/pathology;
*Th17 Cells/immunology/metabolism;
Tumor Necrosis Factor-alpha/blood
- From:Experimental & Molecular Medicine
2012;44(7):424-431
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-alpha. 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.
