Omega-3 fatty acids suppress Th2-associated cytokine gene expressions and GATA transcription factors in mast cells.
Because the interaction between omega-3 fatty acids and mast cells has remained largely unknown in allergies, we investigated whether omega-3 fatty acids affect the activation of mast cells by examining Th2-associated cytokine production and possible molecular mechanisms. Alpha-linolenic acid and its metabolites including eicosapentaenoic acid and decosahexaenoic acid induced a dramatic decrease in the production of interleukin (IL)-4, IL-5 and IL-13 in a dose-dependent manner, as well as mRNA expression of their genes, in activated MC/9 mast cells and bone marrow-derived mast cells. The effects were comparable to those of cyclosporin A (1 μM), a well-known immunosuppressive agent. Nuclear expression of GATA binding protein-1 (GATA-1) and GATA binding protein-2 (GATA-2), essential transcription factors for mast cell activation, was also greatly suppressed. However, their mRNA expressions were not affected. In P815 mast cells, which do not express GATA-1, the suppressive effects on cytokines were abolished. On the contrary, omega-3 fatty acids had less significant effects on IL-4 and IL-5 and resulted in a slight decrease in IL-13 production in EL-4 T cells. Finally, oral administration of fish oil containing high level of omega-3 fatty acids significantly reduced the severity of dermatitis and the thickening of epidermis/dermis in a NC/Nga murine atopic model. The number of cells expressing CD117(+) and FcεRIα(+) was greatly decreased and GATA-1 expression in the cells was also diminished. Taken together, omega-3 fatty acids might target mast cells to a greater extent than T cells to suppress Th2 cytokine expression by inhibiting GATAs for alleviation of allergic disease.
Lab of Pathology, College of Oriental Medicine, Daejeon University, Daejeon, 300-716, Korea.
Bo-Kyung
BK
Park
Sunyoung
S
Park
Jun-Beom
JB
Park
Min Chul
MC
Park
Tae Sun
TS
Min
Mirim
M
Jin
D000818:Animals; D003872:Dermatitis / Q000188:drug therapy / Q000473:pathology; D015536:Down-Regulation; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D018418:Th2 Cells / Q000187:drug effects*
D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D018793:Interleukin-13; D015848:Interleukin-5; D015847:Interleukin-4