生物
白细胞介素8
炎症
基因表达
细胞生物学
趋化因子
内质网
饱和脂肪酸
脂毒性
基因表达调控
基因
生物化学
脂肪酸
内分泌学
免疫学
胰岛素抵抗
胰岛素
作者
Alexander Krogmann,K. Staiger,Carina Haas,Nadja Gommer,Andreas Peter,Martin Heni,Fausto Machicao,Hans‐Ulrich Häring,Harald Staiger
标识
DOI:10.1016/j.mvr.2010.11.008
摘要
Saturated long-chain fatty acids (SFAs) exert unfavourable metabolic effects (lipotoxicity) and induce apoptotic cell death (lipoapoptosis) in certain cell-types. Their contribution to inflammatory cell responses is unclear. We studied the expression of 113 inflammatory genes in human coronary artery endothelial cells (hCAECs) and their regulation by SFAs and unsaturated long-chain fatty acids (UFAs). Gene regulation in hCAECs was assessed with macroarrays, real-time RT-PCR and immunoblotting. Participation of the transcription factor NFκB and the stress kinases JNK and p38 MAPK in gene-regulatory events was examined with pharmacological inhibitors. Based on macroarray data, 59 inflammatory genes were expressed in hCAECs, 14 were regulated by the SFA palmitate. SFA-triggered induction of IL1A, IL6, IL8, CXCL2, CXCL3, CCL20, SPP1 and CEBPB was confirmed by RT-PCR or immunoblotting. All gene inductions were SFA-specific. Using inhibitor SN50, palmitate-induced expression of IL8, CXCL3 and CCL20 was NFκB-dependent (all p<0.05). Furthermore, JNK was involved in palmitate-induced expression of IL1A, IL8, CXCL3, SPP1 and CEBPB as determined with inhibitor SP600125 (all p<0.05). Finally, the effectiveness of the tested fatty acids to induce inflammatory genes was closely reflected by their effectiveness to trigger endoplasmic reticulum stress. In conclusion, hCAECs express a large panel of inflammatory genes with a series of genes being regulated by palmitate and stearate, but not by UFAs. Thus, SFAs represent potential contributors to vascular inflammation.
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