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Effect of Fatty Acids on Interleukin 2 Signaling Pathway in Human Lymphocytes
Author(s) -
Curi Rui,
Gorjão Renata,
CuryBoaventura Maria Fernanda,
de Lima Thais Martins
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1212
Subject(s) - concanavalin a , chemistry , protein kinase b , docosahexaenoic acid , microbiology and biotechnology , propidium iodide , cell growth , endocrinology , medicine , phosphorylation , biochemistry , biology , apoptosis , fatty acid , polyunsaturated fatty acid , programmed cell death , in vitro
The effect of palmitic (PA, C16:0), stearic (SA, C18:0), oleic (OA, C18:1, n‐9), linoleic (LA, C18:2 n‐6), docosahexaenoic (DHA, C22:6 n‐3) and eicosapentaenoic (EPA, C20:5 n‐3) acids on lymphocyte proliferation, cell cycle progression and interleukin −2 (IL‐2) signaling pathway in human lymphocytes was investigated. Human lymphocytes were isolated from heparinized venous blood of normal donors by density‐gradient sedimentation using Histopaque. The cells were stimulated with 5 mg/mL of concanavalin A (ConA) and cultured with fatty acids and IL‐2 (20 ng/mL) for 24 hours. Lymphocyte proliferation was determined by thymidine incorporation and cell cycle was analyzed by flow cytometry using propidium iodide. The cells were stimulated with ConA and treated with IL‐2 and fatty acids for one hour. Afterwards, JAK1 and 3, STAT5 a/b, ERK1/2 and AKT phosphorylation was analyzed by western blotting. PA, SA, DHA and EPA at 50ìM decreased the stimulatory effect of IL‐2 on lymphocyte proliferation, increasing the percentage of cells in G1 phase and decreasing the proportion of cells in S and G2/M phases. OA and LA at 25ìM pronounced the stimulatory effect of IL‐2 on lymphocyte proliferation. PA, SA, DHA and EPA decreased JAK1, JAK3, STAT5 a/b and AKT phosphorylation induced by IL‐2 but OA and LA did not cause any effect. OA and LA increased ERK1/2 phosphorylation and the other fatty acids caused a marked decrease. In conclusion, the inhibitory effect of PA, SA, DHA and EPA on lymphocyte proliferation was due to a decrease in JAK/STAT, ERK and AKT pathway activation. Probably, OA and LA stimulated lymphocyte proliferation by increasing ERK 1/2 phosphorylation. Financial Support: FAPESP, CAPES, and CNPq.