Novel in vitro effects of bucillamine: Inhibitory effects on proinflammatory cytokine production and transendothelial migration of T cells

Yasuhiko Munakata, Satoshi Iwata, Jörg Dobers, Tomonori Ishii, Mamoru Nori, Hirotoshi Tanaka, Chikao Morimoto

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective. To investigate the novel antiinflammatory mechanism of a disease-modifying antirheumatic drug, bucillamine, on activated T cells, specifically its effect on T cell proliferation, cytokine production, and migration of T cells. Methods. T cells were cultured in wells coated with anti-CD3 monoclonal antibodies (mAb) plus anti-CD26 mAb or anti-CD3 plus anti-CD28 mAb, with or without bucillamine. Proliferative responses and the production of interleukin-2 (IL-2), interferon-γ (IFNγ), tumor necrosis factor α (TNFα), IL-6, IL-4, and IL-5 were measured under these costimulatory conditions. Phytohemagglutinin (PHA)-activated T cells were cultured on human umbilical vein endothelial cell-coated transwells in the presence or absence of bucillamine, and T cells migrating through the endothelial cell layer were counted. Immunofluorescence analysis was also performed to analyze the effect of bucillamine on the surface expression of adhesion molecules on T cells. Results. Bucillamine (64 μM) significantly inhibited T cell proliferation and the production of IL-2, IFNγ, TNFα, and IL-6, whereas it had no inhibitory effects on the production of IL-4 and IL-5 in the cultures with anti-CD3 plus anti-CD26 mAb. In contrast, bucillamine had no effects on T cell proliferation or any cytokine production in the cultures with anti-CD3 plus anti-CD28 mAb. Furthermore, the same concentration of bucillamine inhibited transendothelial migration of PHA- activated T cells, and reduced the expression level of CD44 on T cells. Conclusion. This study demonstrated the novel effects of bucillamine in vitro, showing inhibition of type 1 T helper-type cytokine production and proinflammatory cytokine production induced by certain costimulatory conditions, and inhibition of transendothelial migration of T cells. The inhibition of T cell migration appeared to be mediated partly through the reduced expression of CD44, an adhesion molecule on the T cell surface.

Original languageEnglish
Pages (from-to)1616-1623
Number of pages8
JournalArthritis and Rheumatism
Volume43
Issue number7
DOIs
Publication statusPublished - 2000 Jul 1
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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