All-trans-retinoic Acid Suppresses Interferon-gamma and Tumor Necrosis Factor-alpha; a Possible Therapeutic Agent for Rheumatoid Arthritis

Overview

Journal Rheumatol Int

Specialty Rheumatology

Date 2005 Nov 18

PMID 16292516

Citations 11

Authors

Yuji Nozaki

Chise Tamaki

Toshiaki Yamagata

Masafumi Sugiyama

Shinya Ikoma

Koji Kinoshita

Masanori Funauchi

Affiliations

Soon will be listed here.

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)-gamma, interleukin (IL)-2, IL-4, and tumor necrosis factor (TNF)-alpha 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-gamma and TNF-alpha significantly. There were no significant differences between the healthy volunteers and RA patients.

Conclusions: ATRA was demonstrated to affect the cytokine production of IFN-gamma and TNF-alpha. ATRA might be useful in the treatment of autoimmune diseases such as RA.

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