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

Abstract

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 of .50 mM, as observed in our previous study. However, oleic acid (OA; C18:1 n-9) and linoleic acid (LA; C18:2 n-6) increase lymphocyte proliferation at 25 mM. In this study, the effect of these FAs on the 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 mg/ml concanavalin A and treated with FAs in the absence or presence of IL-2 for 1 hour. CD25-a externalization was analyzed by flow cytometry, and Janus kinase 1 ( JAK1), JAK3, signal transducer and activator of transcription (STAT) 5, extracellular signalregulated kinases (ERKs) 1 and 2, Akt, and protein kinase C (PKC)-Z phosphorylation were analyzed by Western blotting. The expression of CD25-a at the cell surface was increased by DHA, SA, and PA but 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 FAs caused a marked decrease. PKC-Z phosphorylation was decreased by OA and LA and was not altered by the remaining FAs. In conclusion, the inhibitory effect of PA, SA, DHA, and EPA on lymphocyte proliferation observed in our previous study was attributable to a decrease in JAK/STAT, ERK, and Akt pathways activated by IL-2. Probably, OA and LA stimulated lymphocyte proliferation by increasing ERK1/2 phosphorylation through PKC-Z activation. The inhibition of JAK1, JAK3, STAT5, ERK1/2, and Akt phosphorylation caused by DHA, SA, and PA is associated with an alteration of CD25 expression at the cell surface.-Gorjão, R., S. M. Hirabara, T. M. de Lima, M. F. Cury-Boaventura, and R. Curi. Regulation of interleukin-2 signaling by fatty acids in human lymphocytes. J. Lipid Res.

Inhibition of IgE production by docosahexaenoic acid is mediated by direct interference with STAT6 and NFκB pathway in human B cells

“…In search of the mechanism we found that DHA decreased the expression of the IL-4Rα chain, thereby explaining at least in part the reduced signaling capacity via the IL-4R mediated by DHA. This reduction of IL-4R expression fits with previous evidence showing decreased IL-2 mediated STAT5 phosphorylation by DHA as a result of reduced surface expression of the IL-2 receptor [55]. This reduced surface expression was the result of an altered lipid raft organization.…”

Perinodal Adipose Tissue and Mesenteric Lymph Node Activation During Reactivated TNBS-Colitis in Rats

“…Myristate does not appear to have the ability to induce cytokine secretion in phorbol ester-differentiated THP-1 cells, and it is much less toxic than stearate at the same concentration [15,16]. On the other hand, stearate induces increased IL-10 production by hepatocytes [17] and inhibits lymphocyte proliferation at non-cytotoxic concentrations [18]. Therefore, we suggest that decreased production of stearate could serve as a pro-inflammatory signal for cytokine production and lymphocyte proliferation.…”

Gene–PUFA interactions and obesity risk

“…Cytokines are a group of modulatory proteins which respond to various stimuli, thereby activating second messengers and signal transduction pathways within the cells (37) . Several cell studies and also dietary intervention studies have shown a reduced production of IL-2 in response to PUFA (16,18,19,38) ; however, the exact mechanism behind this phenomenon still remains unclear (39,40) . In the present study, obesity risk decreased with increasing PUFA content …”