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

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 response 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 response. On the other hand, TPR activation using its agonist enhanced the pro-inflammatory effects of LPS and/or SA. Of note, 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.