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Tocopheryl Phosphate Inhibits Rheumatoid Arthritis-Related Gene Expression In Vitro and Ameliorates Arthritic

Susumu Hama1, Naoko Kirimura2, Aki Obara3

  • 1Faculty of Pharmacy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo 202-8585, Japan.

Molecules (Basel, Switzerland)
|February 25, 2022
PubMed

Insights

Phosphate ester of α-tocopherol (TP) effectively reduces rheumatoid arthritis (RA) progression by inhibiting key RA-related gene expression in fibroblast-like synoviocytes (FLS) and animal models.

Area of Science:

  • Immunology
  • Rheumatology
  • Biochemistry

Background:

  • Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
  • Fibroblast-like synoviocytes (FLS) play a crucial role in RA pathogenesis.
  • The anti-RA effects of α-tocopherol (α-T) are known, but its derivatives' impact on FLS is unclear.

Purpose of the Study:

  • To investigate the effects of α-T and its derivatives, succinic ester of α-T (TS) and phosphate ester of α-T (TP), on RA-related gene expression in FLS.
  • To evaluate the therapeutic potential of TP in an in vivo model of RA.

Main Methods:

  • Fibroblast-like synoviocytes (FLS) were treated with α-T, TS, and TP.
  • Gene expression levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), matrix metalloproteinase (MMP)-3, and MMP-13 were analyzed using RT-PCR.
  • An in vivo laminarin-induced RA mouse model was used to assess TP's therapeutic effects.

Main Results:

  • TP treatment significantly reduced mRNA levels of IL-6, TNF-α, MMP-3, and MMP-13 in FLS without causing cytotoxicity.
  • α-T and TS did not exhibit similar inhibitory effects on these RA-related genes.
  • TP administration ameliorated foot and joint edema and improved arthritis scores in RA model mice.

Conclusions:

  • Phosphate ester of α-tocopherol (TP) demonstrates significant anti-RA properties.
  • TP exerts its anti-RA effects by inhibiting the expression of key RA-associated genes in FLS.
  • TP shows therapeutic potential for treating rheumatoid arthritis.
Keywords:
rheumatoid arthritistocopheryl phosphatetocopheryl succinateα-tocopherol

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