Regulation of IL-2 signaling by fatty acids in human lymphocytes

Renata Gorjão, Sandro Massao Hirabara, Thais Martins de Lima, Maria Fernanda Cury-Boaventura, and Rui Curi

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05580-900

Corresponding Author: renatag{at}icb.usp.br

Docosahexaenoic (DHA, C22:6 n-3), eicosapentaenoic (EPA, C20:5 n-3), palmitic (PA, C16:0) and stearic (SA, C18:0) acids decrease lymphocyte proliferation in concentrations above 50 M as observed in our previous study. However, oleic (OA, C18:1, n-9) and linoleic (LA, C18:2 n-6) acids increase lymphocyte proliferation at 25 M. In the present study, the effect of these fatty acids (FA) on interleukin-2 (IL-2) signaling pathway in human lymphocytes was investigated. Cells were isolated from heparinized venous blood of healthy human donors by density-gradient sedimentation. Cells were stimulated with 5 µg/mL of concanavalin A and treated with FA in the absence or presence of IL-2 for one hour. CD25- externalization was analyzed by flow cytometry and JAK 1, JAK3, STAT 5, ERK 1/2, AKT and PKC- phosphorylation by western blotting. The expression of CD25- in the cell surface was increased by DHA, SA and PA but it was unaffected by EPA, OA and LA. PA, SA, DHA and EPA decreased JAK1, JAK3, STAT5 and AKT phosphorylation induced by IL-2 but OA and LA did not cause any effect. OA and LA increased ERK1/2 phosphorylation whereas the other FA caused a marked decrease. PKC- phosphorylation was decreased by OA and LA and it was not altered by the remaining FA. In conclusion, the inhibitory effect of PA, SA, DHA and EPA on lymphocyte proliferation observed in our previous study was due to a decrease in JAK/STAT, ERK and AKT pathway activated by IL-2. Probably, OA and LA stimulated lymphocyte proliferation by increasing ERK 1/2 phosphorylation throught PKC- activation. The inhibition of JAK1, JAK3, STAT5, ERK1/2 and Akt phosphorylation caused by DHA, SA and PA is associated to an alteration of CD25 expression in cell surface.

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