interleukin-6 regulates anti-arthritic effect of methotrexate via reduction of slc19a1 expression in a mouse arthritis model白细胞介素- 6调节抗风湿作用通过减少甲氨蝶呤slc19a1表达小鼠关节炎模型.pdfVIP
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interleukin-6 regulates anti-arthritic effect of methotrexate via reduction of slc19a1 expression in a mouse arthritis model白细胞介素- 6调节抗风湿作用通过减少甲氨蝶呤slc19a1表达小鼠关节炎模型
Hashizume et al. Arthritis Research Therapy 2012, 14:R96
/content/14/2/R96
RESEARCH ARTICLE Open Access
Interleukin-6 regulates anti-arthritic effect of
methotrexate via reduction of SLC19A1
expression in a mouse arthritis model
1* 1 1 1 2 2
Misato Hashizume , Hiroto Yoshida , Keisuke Tanaka , Miho Suzuki , Isao Matsumoto , Takayuki Sumida and
Masahiko Mihara1
Abstract
Introduction: Methotrexate (MTX) enters cells via the reduced folate carrier SLC19A1, suggesting that SLC19A1 is
associated with the efficacy of MTX. We here examined the relationship between the efficacy of MTX and the
expression of SLC19A1 in glucose 6-phosphate isomerase (GPI)-induced arthritis. We found that interleukin-6 (IL-6)
regulated the expression of SLC19A1, so we studied the effect of a combination of MTX and anti-mouse IL-6
receptor antibody (MR16-1).
Methods: GPI-induced arthritis was induced by intradermal immunization with recombinant GPI. MTX was given
from the first day of immunization. Mice were injected once with MR16-1 10 days after immunization. The levels of
SLC19A1 mRNA in whole hind limbs and immune cells were measured. Synovial cells from arthritic mice were
cultured with cytokines, and cell proliferation and gene expressions were measured.
Results: MTX inhibited the development of GPI-induced arthritis; however, the efficacy of MTX gradually
diminished. SLC19A1 expression in immunized mice with arthritis was lower than in intact mice; moreover,
SLC19A1 expression in arthritic mice was further decreased when they were treated with MTX. IL-6 was highly
expressed in whole hind limbs of arthritic mice. In an in vitro study using synovial cells from arthritic mice, IL-6 +
soluble IL-
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