Eicosapentaenoic acid and docosahexaenoic acid suppress Th2 cytokine expression in RBL-2H3 basophilic leukemia cells.
It is known that the intake of omega-3 fatty acids, such as eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), is beneficial for preventing and/or treating allergic diseases. The pathogenesis of allergic diseases is associated with overactivation of Th2-skewed immunity. Basophils generate large amounts of Th2 cytokines such as interleukin (IL)-4 and IL-13, which are critically involved in allergic inflammation. We investigated how EPA and DHA affect Th2 cytokine expression in phorbol 12-myristate 13-acetate- and ionomycin (PI)-activated RBL-2H3 basophilic leukemia cells. EPA and DHA induced a dramatic decrease in the production of IL-4 and IL-13 and their transcription in a dose-dependent manner. Luciferase assays of RBL-2H3 cells stably expressing Il4 and Il13 promoter-reporter plasmids demonstrated a significant suppression of PI-induced promoter activation. Analysis of certain transcription factors revealed that nuclear expression of c-Fos and the mRNA expression were suppressed by EPA and DHA. Furthermore, they significantly inhibited the nuclear expression and translocation of nuclear factor of activated T cells (NF-AT)1. In contrast, the expression levels of nuclear factor kappa-B (NF-κB), GATA-binding proteins (GATAs), and CCAAT/enhancer binding protein alpha (C/EBPα) were not significantly affected by EPA and DHA. Phosphorylation of extracellular signal-related kinase was inhibited by EPA and DHA, and phosphorylation of p38 mitogen-activated protein kinase was decreased by DHA, but not by EPA. Taken together, our data suggest that EPA and DHA may suppress Th2-skewed allergic immune responses by inhibiting the expression of basophilic IL-4 and IL-13.
1 Laboratory of Pathology, College of Oriental Medicine, Daejeon University , Daejeon, Korea.
Mirim
M
Jin
Sunyoung
S
Park
Bo-Kyung
BK
Park
Jeong June
JJ
Choi
Soo Jeong
SJ
Yoon
Mihi
M
Yang
Myoung Yun
MY
Pyo
D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics* / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D015471:Leukemia, Basophilic, Acute / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
D018793:Interleukin-13; D016328:NF-kappa B; D015847:Interleukin-4; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid