Eicosapentaenoic Acid and Docosahexaenoic Acid Suppress Th2 Cytokine Expression in RBL-2H3 Basophilic Leukemia Cells

• Published in: Journal of medicinal food Vol. 17; no. 2; pp. 198 - 205
• Main Authors: Jin, Mirim, Park, Sunyoung, Park, Bo-Kyung, Choi, Jeong June, Yoon, Soo Jeong, Yang, Mihi, Pyo, Myoung Yun
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.02.2014
• Subjects: basophils; binding proteins; Cell Line, Tumor; docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; dose response; Down-Regulation - drug effects; eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; gene expression; Humans; immune response; inflammation; interleukin-13; Interleukin-13 - genetics; Interleukin-13 - immunology; interleukin-4; Interleukin-4 - genetics; Interleukin-4 - immunology; Leukemia, Basophilic, Acute - drug therapy; Leukemia, Basophilic, Acute - genetics; Leukemia, Basophilic, Acute - immunology; luciferase; messenger RNA; mitogen-activated protein kinase; neoplasm cells; NF-kappa B - genetics; NF-kappa B - immunology; omega-3 fatty acids; pathogenesis; phosphorylation; plasmids; T-lymphocytes; Th2 Cells - drug effects; Th2 Cells - immunology; transcription factor NF-kappa B
• ISSN: 1557-7600; 1557-7600
• DOI: 10.1089/jmf.2013.2935

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.