Limited Applicability of GW9662 to Elucidate PPARγ-Mediated Fatty Acid Effects in Primary Human T-Helper Cells
Jaudszus, A; Lorkowski, S; Gruen, M; Roth, A; Jahreis, G
| HERO ID | 2902568 |
|---|---|
| In Press | No |
| Year | 2014 |
| Title | Limited Applicability of GW9662 to Elucidate PPARγ-Mediated Fatty Acid Effects in Primary Human T-Helper Cells |
| Authors | Jaudszus, A; Lorkowski, S; Gruen, M; Roth, A; Jahreis, G |
| Volume | 2014 |
| Page Numbers | 149628 |
| Abstract | Synthetic antagonists of the nuclear receptor PPARγ such as GW9662 are widely used to elucidate receptor-mediated ligand effects. In addition and complementary to recent work, we examined whether GW9662 is suitable to serve for mechanistic investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC) were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10 μmol/L) 30 min before adding the c9,t11-isomer of conjugated linoleic acid (c9,t11-CLA) as representative of PPARγ-activating fatty acids with immunomodulatory properties. Corresponding cultures were incubated with GW9662 in the absence of the fatty acid. After 19 h, cells were mitogen stimulated for further 5 h. Subsequently, intracellular IL-2 was measured in CD3(+)CD4(+) lymphocytes by means of flow cytometry. 100 μmol/L c9,t11-CLA reduced the number of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty acid effect, likely due to the fact that the compound exerted an own inhibitory effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death in human leukocytes. These results suggest that application of GW9662 is not conducive in this experimental setting. |
| Doi | 10.1155/2014/149628 |
| Pmid | 25054074 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: International journal of inflammation ISSN: 2090-8040 |
| Is Public | Yes |
| Language Text | English |