Inhibition of IgE production by docosahexaenoic acid is mediated by direct interference with STAT6 and NFκB pathway in human B cells.
Nutrition can modify the onset or severity of diseases and recent changes in eating habits are supposed to promote immunoglobulin (Ig) E-dependent disorders. The n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) possesses immunomodulatory properties and has been shown to influence chronic and allergic inflammatory disorders in vivo. Here, we examined the impact of DHA on primary human B cells to elucidate its potential role in direct regulation of IgE production and the underlying mechanisms of action. Therefore, cells were stimulated with anti-CD40/interleukin (IL)-4 in the presence of DHA. Subsequently, Ig production, generation of antibody secreting cells, epsilon-germline transcript (ɛGLT) and activation induced desaminase (AID) expression as well as IgE relevant signaling pathways were analyzed. Our results reveal that DHA inhibits IgE production (75±14%) and, depending on concentration, the differentiation of IgE secreting cells (59±27%). The reduction of IgE is accompanied by a direct inhibition of the switching process indicated by decreased ɛGLT and AID transcription. DHA causes both a reduced CD40 dependent nuclear factor κB-p50 translocation into the nucleus and a decreased IL-4 receptor expression which was associated with a reduction of IL-4 driven signal transducer and activator of transcription 6 phosphorylation. Taken together, DHA inhibits IgE production of human B cells by direct interference with both the CD40 and the IL-4 signaling pathway. The data provide one explanation for the anti-allergic role of DHA at the molecular level.
Weise
Christin
C
Allergy-Center-Charité, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Hilt
Kerstin
K
Milovanovic
Milena
M
Ernst
Dennis
D
Rühl
Ralph
R
Worm
Margitta
M
D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D019013:CD40 Antigens; C508598:IL4 protein, human; C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D052002:NF-kappa B p50 Subunit; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015847:Interleukin-4; D004281:Docosahexaenoic Acids; D007073:Immunoglobulin E