Crosstalk between TLR4-MyD88-NFκB and SCAP-SREBP2 pathways mediates macrophage foam cell formation.

This study was designed to investigate crosstalk between TLR4-MyD88-NFκB and SCAP-SREBP2 pathways in macrophage foam cell formation. Phorbol, 12-myristate, 13-acetate (PMA) activated-THP-1 macrophages were transfected with negative control or MyD88 siRNA. The transfected cells were incubated with LPS in the absence or presence of LDL or IKK inhibitor (BMS-345541). Intracellular cholesterol content was assessed. The mRNA and protein expression of LDLr, HMGCoAR, SCAP and SREBP2 were examined by real-time RT-PCR and Western blotting. The intracellular translocation of SCAP in the organelles was detected by immunofluorecence and confocal microscopy. We demonstrated that LPS induced cholesterol accumulation was attenuated by applying siRNA against MyD88 in the absence or presence of LDL. LPS increased both gene and protein expression of LDLr and HMGCoAR by increasing expression and abnormal translocation of SCAP from the ER to the Golgi. These effects were blocked by knocking down MyD88 or blocking IKK or knocking down SCAP, suggesting that the crosstalk between NFκB and SCAP plays an important role in macrophage foam cell formation and that interfering the crosstalk might be a potential approach in preventing LPS-induced macrophage foam cell formation. PMID: 23335792 [PubMed - as supplied by publisher]
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research