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Mast Cells, T Cells, and Inhibition by Luteolin: Implications for the Pathogenesis and Treatment of Multiple Sclerosis

  • Theoharis C. Theoharides
  • Duraisamy Kempuraj
  • Betina P. Iliopoulou
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 601)

Abstract

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mainly mediated by Th1, but recent evidence indicates that Th2 T cells, mostly associated with allergic reactions, are also involved. Mast cells are involved in allergic and inflammatory reactions because they are located perivascularly and secrete numerous pro-inflammatory cytokines. Brain mast cells are critically placed around the blood–brain barrier (BBB) and can disrupt it, a finding preceding any clinical or pathological signs of MS. Moreover, mast cells are often found close to MS plaques, and the main MS antigen, myelin basic protein (MBP), can activate human cultured mast cells to release IL-8, TNF-α , tryptase, and histamine. Mast cells could also contribute to T cell activation since addition of mast cells to anti-CD3/anti-CD28 activated T cells increases T cell activation over 30-fold. This effect requires cell-to-cell contact and TNF, but not histamine or tryptase. Pretreatment with the flavone luteolin totally blocks mast cell stimulation and T cell activation. Mast cells could constitute a new unique therapeutic target for MS.

Keywords

Multiple Sclerosis Mast Cell Myelin Basic Protein Human Mast Cell Central Nervous System Inflammation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Theoharis C. Theoharides
    • 1
  • Duraisamy Kempuraj
    • 1
  • Betina P. Iliopoulou
    • 1
  1. 1.Departments of Pharmacology and Experimental Therapeutics; Internal Medicine and Biochemistry; Immunology ProgramTufts University School of Medicine and Tufts-New England Medical CenterBostonUSA

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