Mast cells, T cells, and inhibition by luteolin: implications for the pathogenesis and treatment of multiple sclerosis.
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 proinflammatory 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-alpha, 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.
Theoharides
Theoharis C
TC
Department of Pharmacology, Internal Medicine and Biochemistry, Immunology Program, Tufts University School of Medicine, Tufts-New England Medical Center, Boston, MA, USA. theoharis.theoharides@tufts.edu
Kempuraj
Duraisamy
D
Iliopoulou
Betina P
BP
D018106:CD28 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D005419:Flavonoids / Q000737:chemistry; D006801:Humans; D047311:Luteolin / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D008954:Models, Biological; D008956:Models, Chemical; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D018106:CD28 Antigens; D017252:CD3 Complex; D005419:Flavonoids; D047311:Luteolin