Atherogenic High Fat/High Cholesterol Diet Induces Tlrs-associated Pulmonary Inflammation In C57BL/6J Mice

Background: Recent reports showed pulmonary inflammation inseveral lipid metabolism related gene knock out mice. However, the effectsof atherogenic high fat/high cholesterol diet induced dyslipidemia on thehomeostasis of wild C57BL/6J mice lung were poorly discovered.Objective: To explore the effects of atherogenic high fat/highcholesterol diet induced dyslipidemia on the homeostasis of wild C57BL/6Jmice lung, and discuss the related mechanism.Methods: sixty6-week-old male C57BL/6J mice were randomlydivided into two groups and treated with regular diet or atherogenic highfat/high cholesterol diet respectively. After12and16weeks feeding,pulmonary lipid deposition were assessed with Oil red O staining.Inflammation in lung were detected by hematoxylin and eosin (H&E) andimmunohistochemistry (IHC). Gene expression and protein levels weredetermined by quantitative Polymerase chain reaction(qPCR)and westernblotting. Secretory levels of inflammatory cytokines were assayed byEnzyme-linked immumosorbent assay(ELISA)kits. Results: Hypercholesterolemia and pulmonary lipid accumulationwere progressively exacerbated in atherogenic high fat/high cholesterol diettreated C57BL/6J mice, and the results of transmission electron microscopysuggested that the alveolar type II epithelial cell was one of the target celltypes for the pulmonary lipid accumulation. Compared with regular diet fedmice, the lungs of atherogenic high fat/high cholesterol diet fed mice showeddistinctive signs of inflammation that included macrophage accumulation,lymphocyte infiltration and elevated levels of proinflammatory cytokineslike Tumor necrosis factor α(TNFa)and Monocyte chemotactic protein-1(MCP-1). Consistently, the mRNA and protein expression of TLR2andTLR4were significantly up-regulated, and the translocation of NFκB intonucleus was activated in atherogenic high fat/high cholesterol diet fed micelung. In addition, as the ligands of TLRs, oxidized low-density lipoprotein(oxLDL) up-regulated the expression of TLR2and TLR4inA549cell.Conclusions: The findings suggest that the atherogenic high fat/highcholesterol diet promote lipid accumulation and chronic inflammation in thelung of C57BL/6J mice. It may partly due to the activation of TLRs/NFκBpathway triggered by disturbance of lipid metabolism in the lung.