Curcumin, a constituent of curry, suppresses IgE-mediated allergic response and mast cell activation at the level of Syk.
BACKGROUND
Activation of mast cells through the high-affinity receptor for IgE (FcepsilonRI) underlies atopic allergic reactions. Curcumin can block this activation, but the mechanism and the effects of curcumin on IgE-mediated allergic reactions are unknown.


OBJECTIVE
We sought to determine the antiallergic activity of curcumin in vivo and its mechanism of action in mast cells.


METHODS
The antiallergic activity of curcumin was evaluated in mast cell cultures and the passive cutaneous anaphylaxis model. The effects of curcumin on mast cell signaling events were examined by using immunoblotting, immunoprecipitation, RT-PCR, and other molecular biologic approaches.


RESULTS
Curcumin inhibited antigen-mediated activation of mast cells and passive cutaneous anaphylaxis in mice. Suppression of degranulation and secretion of TNF-alpha and IL-4 was apparent at concentrations as low as 3 micromol/L curcumin in activated mast cells. Similar concentrations of curcumin suppressed Syk-dependent phosphorylations of the adaptor proteins linker of activated T cells and Grb2-associated binder 2, which are critical for mast cell activation. Although curcumin did not inhibit the phosphorylation of Syk itself, it directly inhibited Syk kinase activity in vitro. Further downstream, activating phosphorylations of Akt and the mitogen-activated protein kinases p38, p44/42 (extracellular signal-regulated kinase 1/2), and c-Jun N-terminal kinase, which are critical for the production of inflammatory cytokines, were also inhibited.


CONCLUSIONS
Curcumin inhibits Syk kinase-dependent signaling events in mast cells and might thus contribute to its antiallergic activity. Therefore curcumin might be useful for the treatment of mast cell-related immediate and delayed allergic diseases.
Lee
Jun Ho
JH
Department of Immunology and physiology, College of Medicine, Konkuk University, Chungju, Korea.
Kim
Jie Wan
JW
Ko
Na Young
NY
Mun
Se Hwan
SH
Her
Erk
E
Kim
Bo Kyung
BK
Han
Jeung Whan
JW
Lee
Hoi Young
HY
Beaven
Michael A
MA
Kim
Young Mi
YM
Choi
Wahn Soo
WS
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015550:Cell Degranulation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D047468:Immunoprecipitation; D015847:Interleukin-4 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D018926:Anti-Allergic Agents; D047908:Intracellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D003474:Curcumin