BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats

Shan Shan Song, Bei Huang, Qingtong Wang, Yu Jing Wu, Jing Jing Fu, Yun Fang Zhang, Yan Chang, Jing Yu Chen, Hua Xun Wu, Di Wang, Ling Ling Zhang, Wei Wei

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalActa Pharmacologica Sinica
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2013
Externally publishedYes

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Receptors, Tumor Necrosis Factor, Type II
Recombinant Fusion Proteins
Experimental Arthritis
T-Lymphocytes
Arthritis
T-Lymphocyte Subsets
Therapeutic Uses
Messenger RNA
Joints
Cytokines
Intradermal Injections
Metatarsal Bones
Ankle Joint
Interleukin-17
Freund's Adjuvant
Drug and Narcotic Control
Emulsions
Matrix Metalloproteinases
Interleukin-1
Methotrexate

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 journalArticle

Song, SS, Huang, B, Wang, Q, Wu, YJ, Fu, JJ, Zhang, YF, Chang, Y, Chen, JY, Wu, HX, Wang, D, Zhang, LL & Wei, W 2013, 'BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats', Acta Pharmacologica Sinica, vol. 34, no. 3, pp. 414-423. https://doi.org/10.1038/aps.2012.171
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. / BF02, a recombinant TNFR2 fusion protein, alleviates adjuvant arthritis by regulating T lymphocytes in rats. In: Acta Pharmacologica Sinica. 2013 ; Vol. 34, No. 3. pp. 414-423.
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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.",
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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

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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.

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KW - adjuvant arthritis

KW - BF02

KW - cytokine

KW - inflammation

KW - methotrexate

KW - T lymphocytes

KW - TNF-α

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