Blocking Thromboxane-Prostanoid Receptor Signaling Attenuates Lipopolysaccharide- and Stearic Acid-Induced Inflammatory Response in Human PBMCs

被引:2
作者
Rajamanickam, Vinothkumar [1 ,2 ]
Desouza, Cyrus V. [1 ,2 ]
Castillo, Romilia T. [1 ,2 ]
Saraswathi, Viswanathan [1 ,2 ]
机构
[1] Univ Nebraska Med Ctr, Dept Internal Med, Div Diabet Endocrinol & Metab, Omaha, NE 68198 USA
[2] VA Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE 68105 USA
关键词
thromboxane A2; inflammation; lipopolysaccharide; stearic acid; PBMC; ROCK; SYNTHASE INHIBITOR; DIABETES-MELLITUS; ANTAGONIST; ACTIVATION; OBESITY; MECHANISM; CELLS;
D O I
10.3390/cells13161320
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Inflammation is implicated in the etiology of obesity-related diseases. Thromboxane-prostanoid receptor (TPR) is known to play a role in mediating an inflammatory response in a variety of cells. Gut-derived lipopolysaccharide (LPS), a TLR4 agonist, is elevated in obesity. Moreover, free fatty acids (FFAs) are important mediators of obesity-related inflammation. However, the role and mechanisms by which TPR regulates the inflammatory response in human immune cells remain unclear. We sought to determine the link between TPR and obesity and the role/mechanisms by which TPR alters LPS- or stearic acid (SA)-induced inflammatory responses in PBMCs. Cells were pre-treated with agents blocking TPR signaling, followed by treatment with LPS or stearic acid (SA). Our findings showed that TPR mRNA levels are higher in PBMCs from individuals with obesity. Blockade of TPR as well as ROCK, which acts downstream of TPR, attenuated LPS- and/or SA-induced pro-inflammatory responses. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, the TPR agonist by itself elicits an inflammatory response, which was attenuated by blocking TPR or ROCK. Our data suggest that TPR plays a key role in promoting an inflammatory response in human PBMCs, and this effect is mediated via TLR4 and/or ROCK signaling.
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页数:13
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