Abstract
Aim:To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function.Methods:SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets.Results:In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3 + CD4 + and CD4 + CD25 + T lymphocytes were increased, whereas the percentages of CD4 + CD62L + and CD4 + CD25+ FoxP3 + T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets.Conclusion:BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 414-423 |
| Number of pages | 10 |
| Journal | Acta Pharmacologica Sinica |
| Volume | 34 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2013 |
| Externally published | Yes |
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Keywords
- adjuvant arthritis
- BF02
- cytokine
- inflammation
- methotrexate
- T lymphocytes
- TNF-α
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats. / Song, Shan Shan; Huang, Bei; Wang, Qingtong; Wu, Yu Jing; Fu, Jing Jing; Zhang, Yun Fang; Chang, Yan; Chen, Jing Yu; Wu, Hua Xun; Wang, Di; Zhang, Ling Ling; Wei, Wei.
In: Acta Pharmacologica Sinica, Vol. 34, No. 3, 01.03.2013, p. 414-423.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats
AU - Song, Shan Shan
AU - Huang, Bei
AU - Wang, Qingtong
AU - Wu, Yu Jing
AU - Fu, Jing Jing
AU - Zhang, Yun Fang
AU - Chang, Yan
AU - Chen, Jing Yu
AU - Wu, Hua Xun
AU - Wang, Di
AU - Zhang, Ling Ling
AU - Wei, Wei
PY - 2013/3/1
Y1 - 2013/3/1
N2 - Aim:To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function.Methods:SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets.Results:In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3 + CD4 + and CD4 + CD25 + T lymphocytes were increased, whereas the percentages of CD4 + CD62L + and CD4 + CD25+ FoxP3 + T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets.Conclusion:BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.
AB - Aim:To investigate the therapeutic effects of BF02 on adjuvant arthritis (AA) in rats and the regulatory effects of BF02 on T lymphocyte function.Methods:SD rats received a single intradermal injection of Freund's complete adjuvant emulsion into the right hind metatarsal footpad. After the onset of AA, the rats were injected BF02 (1, 3, or 9 mg/kg, sc) every 3 d for a total of 15 d. Intragastric administration of methotrexate (MTX, 0.5 mg/kg, every 3 d for a total of 15 d) was taken as the positive control drug. Arthritis index, swollen joint count, ankle joint histopathology, spleen histopathology and the paw radiography were used for evaluating the drug effects on AA rats. T lymphocyte function was assessed by measuring T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression levels, and percentage of T lymphocyte subsets.Results:In the AA rats, remarkable secondary inflammatory responses exhibited, accompanied by significantly higher levels of IL-1, IL-6, TNF-α, IL-17, LTα, RANKL, and MMP-13. The expression of IL17 and TNF-α mRNAs was also substantially higher than in normal rats. The percentages of CD3 + CD4 + and CD4 + CD25 + T lymphocytes were increased, whereas the percentages of CD4 + CD62L + and CD4 + CD25+ FoxP3 + T lymphocytes were decreased. Treatment of the AA rats with BF02 (9 mg/kg) or MTX significantly decreased the arthritis index, swollen joint count and arthritis global assessment. Moreover, both BF02 (9 mg/kg) and MTX significantly inhibited T lymphocyte proliferation, and blocked the above mentioned aberrance in T lymphocyte cytokine levels, IL17 and TNF-α mRNA expression, and percentages of T lymphocyte subsets.Conclusion:BF02 exerts therapeutic effects on AA rats via the regulation of T lymphocytes.
KW - adjuvant arthritis
KW - BF02
KW - cytokine
KW - inflammation
KW - methotrexate
KW - T lymphocytes
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=84874589746&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874589746&partnerID=8YFLogxK
U2 - 10.1038/aps.2012.171
DO - 10.1038/aps.2012.171
M3 - Article
C2 - 23377547
AN - SCOPUS:84874589746
VL - 34
SP - 414
EP - 423
JO - Acta Pharmacologica Sinica
JF - Acta Pharmacologica Sinica
SN - 1671-4083
IS - 3
ER -