TLR4 overexpression enhances saturated fatty acid–induced inflammatory cytokine gene expression in sheep:

European Journal of Inflammation

XueXu¹ 

关键词: genetically modified sheep;    inflammatory cytokine;    saturated fatty acids;    Toll-like receptor 4;   

DOI  :  10.1177/2058739218792976

学科分类：医学（综合）

来源: Sage Journals

【 摘 要 】

Saturated fatty acids (SFAs) can directly stimulate innate immune responses, thereby exacerbating inflammatory aspects of metabolic syndrome. Dietary SFAs act as ligands of Toll-like receptor 4 (TLR4), triggering associated signaling pathways. In this study, we investigated the role of TLR4 in palm oil SFA-associated inflammatory cytokine gene expression in monocytes/macrophages and adipose tissue using TLR4-overexpressing genetically modified sheep. SFA stimulation resulted in upregulation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ), and interleukin-10 (IL-10), and TLR4 overexpression enhanced such SFA-induced inflammatory cytokine expression. Moreover, SFAs markedly activated MyD88-dependent signaling, including IL-1 receptor–associated kinase 4 (IRAK4), TNF receptor–associated factor 6 (TRAF6), and nuclear factor-κB (NF-κB). Taken together, our results indicate that TLR4 overexpression enhances the SFA-induced inflammatory response through MyD88-dependent signaling in monocytes/macrophages and adipose tissue.

【 授权许可】

CC BY-NC