Atherogenic high cholesterol/high fat diet induces TLRs-associated pulmonary inflammation in C57BL/6J mice

To explore the effects of high cholesterol/high fat diet-induced hypercholesterolemia on pulmonary homeostasis of wild-type C57BL/6J mice. Six- to eight-week-old male C57BL/6J mice were randomly divided into two groups and treated with either high cholesterol/high fat diet (HCD, containing 20 % fat, 1.25 % cholesterol and 0.5 % sodium cholate) or a matching regular diet (RD, containing 4 % fat with no cholesterol and cholate added) for 12-16 weeks. Twelve to sixteen weeks after HCD diet feeding, hypercholesterolemia and pulmonary lipid accumulation were progressively exacerbated in C57BL/6J mice. Meanwhile, the HCD-fed mice showed distinctive signs of inflammation in the lung, which includes macrophage accumulation in alveolar lumen and lymphocyte infiltration around perivascular area. Simultaneously, the mRNA and protein expression of TLR2 and TLR4 were significantly up-regulated, and the translocation of NF kappa B into nucleus was activated in HCD-fed mice lung. In vitro, oxidized low-density lipoprotein (oxLDL) could directly up-regulate the expression of TLR2 and TLR4 in both A549 and MLE-12 lung epithelial cell lines. These findings suggested that high cholesterol/high fat diet-induced hypercholesterolemia could result in TLRs/NF kappa B pathway-associated low-grade pulmonary inflammation in C57BL/6J mice, which might alter the lung's immune responsiveness to a variety of environmental exposures.