The hydroxyflavone, fisetin, suppresses mast cell activation induced by interaction with activated T cell membranes.
OBJECTIVE
Cell-to-cell interactions between mast cells and activated T cells are increasingly recognized as a possible mechanism in the aetiology of allergic or non-allergic inflammatory disorders. To determine the anti-allergic effect of fisetin, we examined the ability of fisetin to suppress activation of the human mast cell line, HMC-1, induced by activated Jurkat T cell membranes.


METHODS
HMC-1 cells were incubated with or without fisetin for 15 min and then co-cultured with Jurkat T cell membranes activated by phorbol-12-myristate 13-acetate for 16 h. We determined gene expression in activated HMC-1 cells by DNA microarray and quantitative reverse transcription (RT)-PCR analysis. We also examined activation of the transcription factor NF-kappaB and MAP kinases (MAPKs) in activated HMC-1 cells.


RESULTS
Fisetin suppresses cell spreading and gene expression in HMC-1 cells stimulated by activated T cell membranes. Additionally, we show that these stimulated HMC-1 cells expressed granzyme B. The stimulatory interaction also induced activation of NF-kappaB and MAPKs; these activations were suppressed by fisetin. Fisetin also reduced the amount of cell surface antigen CD40 and intercellular adhesion molecule-1 (ICAM-1) on activated HMC-1 cells.


CONCLUSIONS
Fisetin suppressed activation of HMC-1 cells by activated T cell membranes by interfering with cell-to-cell interaction and inhibiting the activity of NF-kappaB and MAPKs and thereby suppressing gene expression. Fisetin may protect against the progression of inflammatory diseases by limiting interactions between mast cells and activated T cells.
Nagai
K
K
National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
Takahashi
Y
Y
Mikami
I
I
Fukusima
T
T
Oike
H
H
Kobori
M
M
D019013:CD40 Antigens / Q000096:biosynthesis; D015550:Cell Degranulation; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D053804:Granzymes / Q000096:biosynthesis; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D054353:Perforin / Q000096:biosynthesis; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure
D019013:CD40 Antigens; D005419:Flavonoids; D044948:Flavonols; D016328:NF-kappa B; D054353:Perforin; D018799:Intercellular Adhesion Molecule-1; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D053804:Granzymes; C017875:fisetin
Biochem J. 2004 Apr 15;379(Pt 2):409-20
14741045
Mol Cell Biol. 2008 Oct;28(20):6208-22
18694960
J Exp Med. 1996 May 1;183(5):2129-42
8642323
Pharmacol Res. 2007 Jan;55(1):31-7
17079162
J Allergy Clin Immunol. 2007 Jul;120(1):48-55
17482668
Leuk Res. 2003 Aug;27(8):677-82
12801524
J Biol Chem. 2005 Jun 24;280(25):23549-58
15843372
Immunol Rev. 2000 Feb;173:131-40
10719674
Arch Pharm Res. 2008 Oct;31(10):1303-11
18958421
Br J Pharmacol. 2007 Jul;151(6):725-36
17471178
Cell Mol Life Sci. 2007 Oct;64(19-20):2690-701
17878996
Blood. 2005 Dec 15;106(13):4241-8
16123219
Nature. 1998 Jun 4;393(6684):478-80
9624004
Clin Exp Allergy. 2004 Nov;34(11):1725-31
15544597
Allergy. 2006 Mar;61(3):289-97
16436136
J Leukoc Biol. 2005 Jun;77(6):975-83
15784689
J Exp Med. 2000 Nov 20;192(10):1441-52
11085746
J Allergy Clin Immunol. 2000 Mar;105(3):500-5
10719300
Nature. 1998 Jun 4;393(6684):474-8
9624003
Biochim Biophys Acta. 2003 Dec 7;1643(1-3):75-83
14654230
Br J Haematol. 2001 Sep;114(3):616-23
11552987
Cell Death Differ. 2007 Oct;14(10):1768-79
17599099
J Leukoc Biol. 2005 Jul;78(1):239-47
15800027
J Clin Invest. 2006 Oct;116(10):2748-56
16964309
Nature. 2008 Jul 24;454(7203):445-54
18650915
Cell. 1994 Mar 25;76(6):977-87
8137431
Mol Immunol. 2007 Jul;44(14):3462-72
17485116
Arterioscler Thromb Vasc Biol. 2004 Dec;24(12):2245-50
15472125
Blood. 2006 Oct 1;108(7):2290-9
16794249
Proc Natl Acad Sci U S A. 2005 May 3;102(18):6467-72
15840716
Trends Immunol. 2007 Aug;28(8):360-5
17625970
J Agric Food Chem. 2008 Jun 11;56(11):4004-11
18489106
J Pharmacol Sci. 2003 Jul;92(3):291-5
12890895
J Leukoc Biol. 1998 Mar;63(3):337-41
9500521
Nat Prod Rep. 2004 Aug;21(4):539-73
15282635
J Exp Med. 1994 Nov 1;180(5):1889-900
7964465
Am J Respir Cell Mol Biol. 2004 Sep;31(3):283-91
15191916
Pharmacol Rev. 2000 Dec;52(4):673-751
11121513
Immunol Today. 1996 Feb;17(2):60-3
8808051
Nat Rev Immunol. 2006 Mar;6(3):218-30
16470226
Allergy. 2005 Oct;60(10):1316-9
16135000
Br J Pharmacol. 2007 Oct;152(3):299-303
17618310
Int Arch Allergy Immunol. 2004 Jun;134(2):135-40
15153793
J Allergy Clin Immunol. 1997 Feb;99(2):155-60
9042038
Leuk Res. 1988;12(4):345-55
3131594
J Nutr. 2000 Sep;130(9):2243-50
10958819
Nature. 1994 Aug 25;370(6491):650-2
7520535
J Exp Med. 2000 Mar 6;191(5):813-22
10704463
Allergy. 2008 Jun;63(6):703-11
18070228
J Interferon Cytokine Res. 1997 Mar;17(3):167-76
9085942
J Immunol. 2003 Apr 15;170(8):4325-34
12682269
J Immunol. 2001 Oct 1;167(7):4008-16
11564820
J Allergy Clin Immunol. 2008 Feb;121(2):448-455.e5
18028996
Allergol Int. 2007 Jun;56(2):113-23
17384531
Nature. 1998 Jun 4;393(6684):480-3
9624005
J Immunol. 2004 Jun 15;172(12):7459-65
15187124
Blood. 2005 Nov 1;106(9):3114-22
16020513
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10599-603
7479848
J Immunol. 1998 Apr 15;160(8):4026-33
9558112
J Allergy Clin Immunol. 1985 Jul;76(1):70-82
2409123
Curr Opin Immunol. 2007 Dec;19(6):687-93
17761410