Liver X receptor activation protects against inflammation and enhances autophagy in myocardium of neonatal mouse challenged by lipopolysaccharides

Abstract

Liver X receptors (LXRs) has been emerged as negative regulators of cardiomyocytic inflammation. The cellular process of autophagy is believed to play a protective role in myocardium during the inflammatory status. In this study, we investigated the role of LXRs agonist TO901317 (TO) on lipopolysaccharides (LPS)-induced myocardial inflammation and autophagy. The results showed that TO pretreatment significantly reduced the LPS-induced infiltration of inflammatory cells, elevation of NF-κB protein, TNF-α, and IL-6 mRNA levels in the myocardium. Moreover, LPS stimulated autophagy in neonatal mice heart, and this effect was further enhanced by TO pretreatment as evidenced by increased LC3-II/ GAPDH ratio increment. Furthermore, TUNEL assay revealed LPS stimulation also increased the number of apoptotic cells in the myocardium, and the increment was inhibited by TO pretreatment. Our findings suggested that attenuation of inflammation and apoptosis, and enhancement of autophagy by TO may contribute to the protection of myocardium under inflammatory condition.

Globular Adiponectin Causes Tolerance to LPS-Induced TNF-α Expression via Autophagy Induction in RAW 264.7 Macrophages: Involvement of SIRT1/FoxO3A Axis

“…In particular, autophagy has been shown to play a critical role in the regulation of inflammatory responses. For example, the induction of autophagy has been found to be aligned with attenuation of LPS-induced inflammation [ 45 ] and inhibition of autophagy contributes to the augmentation of TNF-α and IL-1β expression in LPS-stimulated intestinal epithelium [ 46 ], suggesting the critical role of autophagy in suppressing inflammatory responses. In addition, autophagy plays a cytoprotective role in LPS-induced acute kidney disease [ 47 ].…”

Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling

“…Meanwhile, LC3I is usually converted to LC3II during the formation of autophagosome [40]. More importantly, according to the previous works [41, 42], levels of LC3-II should be compared not to LC3-I but ideally to more than one “housekeeping” protein in autophagy detection and LC3 assays should be evaluated with and without autophagy inhibitor (3-MA) [27]. As expected, CLP significantly inhibited the ratio of LC3-II/GAPDH and Beclin-1 level, and this effect was abolished by Emodin.…”

Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ ‐mediated suppression of the host cholesterol transport protein ABCA1

“…First, high cholesterol has been shown to inhibit autophagic flux by sequestering the SNARE proteins required for autophagosome/lysosome fusion (Barbero-Camps et al, 2018;Fraldi et al, 2010). Flux can be restored by depletion of cholesterol with methyl-β-cyclodextrin or T090187 treatment (Dai et al, 2017;Liu et al, 2014), suggesting that cholesterol accumulation may protect the bacteria from autophagic clearance. Furthermore, cholesterol delivery from the ER to the cytoplasmic leaflet of endolysosomes via OSBP promotes the recruitment and activation of mTORC1, leading to suppression of autophagy (Lim et al, 2019).…”

“…The gentamicin resistance assay has been described previously (Liu et al, 2014). Briefly, cells were seeded at 1 Â 10 5 cells/well onto 24-well culture dishes 18 h prior to infection at an MOI of 75.…”