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All-trans-retinoic acid suppresses interferon-γ and tumor necrosis factor-α; a possible therapeutic agent for rheumatoid arthritis

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Abstract

Objectives: To study the effects of all-trans-retinoic acid (ATRA), we determined the proliferation and cytokine production by peripheral blood mononuclear cells (PBMCs) and CD4+ T cells in healthy volunteers and patients with rheumatoid arthritis (RA), and explored the possibility of using ATRA as a therapeutic agent for autoimmune diseases. Methods: Proliferation of these cells was determined by modified MTT assay, and expression of CC chemokine receptors 4 (CCR4) and CCR5 was determined by flow cytometry. Production and expression of interferon (IFN)-γ, interleukin (IL)-2, IL-4, and tumor necrosis factor (TNF)-α was determined by Enzyme-Linked Immunosorbent Assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). The presence of STAT6 protein was determined by Western blot analysis. Results: ATRA did not affect the proliferation or production of IL-2 and IL-4. We did not detect STAT6 protein, and saw no evidence of the differentiation of PBMCs to Th1 or Th2 cells. In contrast, ATRA suppressed the production of IFN-γ and TNF-α significantly. There were no significant differences between the healthy volunteers and RA patients. Conclusions: ATRA was demonstrated to affect the cytokine production of IFN-γ and TNF-α. ATRA might be useful in the treatment of autoimmune diseases such as RA.

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Acknowledgment

We are grateful to K. Niki and K. Furukawa for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Nephrology and Rheumatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Osaka, Japan

    Yuji Nozaki, Chise Tamaki, Toshiaki Yamagata, Masafumi Sugiyama, Shinya Ikoma, Koji Kinoshita & Masanori Funauchi

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  1. Yuji Nozaki
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  2. Chise Tamaki
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  3. Toshiaki Yamagata
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  4. Masafumi Sugiyama
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  5. Shinya Ikoma
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  6. Koji Kinoshita
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  7. Masanori Funauchi
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Correspondence to Masanori Funauchi.

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Nozaki, Y., Tamaki, C., Yamagata, T. et al. All-trans-retinoic acid suppresses interferon-γ and tumor necrosis factor-α; a possible therapeutic agent for rheumatoid arthritis. Rheumatol Int 26, 810–817 (2006). https://doi.org/10.1007/s00296-005-0076-1

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  • DOI: https://doi.org/10.1007/s00296-005-0076-1

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