Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell-dependent stimulation of Jurkat T cells.
OBJECTIVE
Allergic inflammation and autoimmune diseases, such as atopic dermatitis, psoriasis and multiple sclerosis (MS), involve both mast cell and T-cell activation. However, possible interactions between the two and the mechanism of such activations are largely unknown.


METHODS
Human umbilical cord blood-derived cultured mast cells (hCBMCs) and Jurkat T cells were incubated separately or together, following activation with myelin basic protein (MBP), as well as with or without pretreatment with the flavonoid luteolin for 15 min. The supernatant fluid was assayed for inflammatory mediators released from mast cells and interleukin (IL)-2 release from Jurkat cells.


RESULTS
MBP (10 microM) stimulates hCBMCs to release IL-6, IL-8, transforming growth factor (TGF)-beta1, tumour necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), histamine and tryptase (n=6, P<0.05). Addition of mast cells to Jurkat cells activated by anti-CD3/anti-CD28 increases IL-2 release by 30-fold (n=3, P<0.05). MBP-stimulated mast cells and their supernatant fluid further increase Jurkat cell IL-2 release (n=3, P<0.05). Separation of mast cells and activated Jurkat cells by a Transwell permeable membrane inhibits Jurkat cell stimulation by 60%. Pretreatment of Jurkat cells with a TNF-neutralizing antibody reduces IL-2 release by another 40%. Luteolin pretreatment inhibits mast cell activation (n=3-6, P<0.05), Jurkat cell activation and mast cell-dependent Jurkat cell stimulation (n=3, P<0.05).


CONCLUSIONS
Mast cells can stimulate activated Jurkat cells. This interaction is inhibited by luteolin, suggesting that this flavonoid may be useful in the treatment of autoimmune diseases.
Kempuraj
D
D
Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA.
Tagen
M
M
Iliopoulou
B P
BP
Clemons
A
A
Vasiadi
M
M
Boucher
W
W
House
M
M
Wolfberg
A
A
Theoharides
T C
TC
D002478:Cells, Cultured; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells / Q000187:drug effects* / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D004676:Myelin Basic Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053802:Tryptases / Q000187:drug effects / Q000378:metabolism
D018836:Inflammation Mediators; D007376:Interleukin-2; D004676:Myelin Basic Protein; D053802:Tryptases; D047311:Luteolin