Protective effect of liver X receptor on cigarette smoke and lipopolysaccharide induced airway inflammation and emphysema in mice.

OBJECTIVE: The aim of this study is to assess the impact of Liver X receptors (LXRs) on airway inflammation, airway remodeling, and lipid deposition induced by cigarette smoke and lipopolysaccharide (LPS) exposure in the lung. METHODS: Wild mice and LXR-deficient mice were exposed to cigarette smoke and LPS to induce airway inflammation and remodeling. In addition, some wild mice received intraperitoneal treatment with the LXR agonist GW3965 before exposure to cigarette smoke and LPS. Lung tissue and bronchoalveolar lavage fluid were collected to evaluate airway inflammation, airway remodeling and lipid deposition. RESULTS: Exposure to cigarette smoke and LPS resulted in airway inflammation, emphysema and lipid accumulation in wild mice. These mice also exhibited downregulated LXRα and ABCA1 in the lung. Treatment with GW3965 mitigated inflammation, remodeling and lipid deposition, while the deletion of LXRs exacerbated these effects. Furthermore, GW3965 treatment following exposure to cigarette smoke and LPS increased LXRα and ABCA1 expression and attenuated MyD88 expression in wild mice. CONCLUSION: LXRs demonstrate the potential to mitigate cigarette smoke and LPS- induced airway inflammation, emphysema and lipid disposition in mice.

Effects of liver X receptor in O3-induced airway inflammation and remodeling in mice.

Background: The current clinical treatment of chronic obstructive pulmonary disease (COPD) mainly uses drugs to improve symptoms, but these drugs cannot reverse the progression of the disease and the pathological changes in lung tissue. This study aimed to investigate the effects and mechanisms of Liver X receptors (LXRs) in ozone (O3)-induced airway inflammation and remodeling in mice. Methods: Wild mice and LXR deficient mice were exposed to O3 twice a week for 6 weeks. Some wild mice were intraperitoneally injected with T0901317 (a LXR agonist) before O3 exposure. Wild mice were exposed to ambient air and intraperitoneally injected with normal saline (NS) as control group. The lung tissues and bronchoalveolar lavage fluid (BALF) were collected to evaluate airway inflammation, airway remodeling and lipid disorder. Results: After O3 exposure, LXR deficient mice showed severe airway inflammation and airway remodeling compared with the wild mice. There were a lot of foamy macrophages appeared in BALF of LXR deficient mice. The inflammatory proteins such as myeloid differentiation primary response protein 88 (MyD88) and interleukin-1 receptor-associated kinase (IRAK) in the lung tissues of LXR deficient mice were significantly increased compared with the wild mice. In wild mice exposed to O3, T0901317 treatment can alleviate airway inflammation, airway remodeling and foamy macrophages in BALF. And MyD88 and IRAK expression in lung tissue were also attenuated by T0901317 treatment. Conclusions: LXRs play protective roles in O3-induced lipid accumulation, airway inflammation and airway remodeling.

Long Noncoding RNA LINC00551 Suppresses Glycolysis and Tumor Progression by Regulating c-Myc-Mediated PKM2 Expression in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a leading cause of mortality associated with cancer globally. Thus, it is essential to elucidate its tumorigenesis and prognosis. Accumulating evidence shows that long noncoding RNAs (lncRNAs) play important roles in the occurrence and progression of tumors by regulating their glucose metabolism. METHODS: Bioinformatics analysis was performed to explore the expression of LINC00551 in LUAD. The level of LINC00551 in LUAD cells and tissues was detected by RT-qPCR. CCK-8, colony formation, EDU and transwell assays were conducted to evaluate the cell growth and migration of LUAD cells (A549 and PC9). High throughput sequencing was used to discover the downstream genes of LINC00551. The metabolic function of LUAD cells was identified by glucose uptake and lactate production assays. Furthermore, tumor xenografts were established to investigate the effects of LINC00551 on tumor growth in vivo. RESULTS: Herein, we found that LINC00551 was low-expressed in LUAD, and its level correlated with clinical prognosis. Ectopic expression of LINC00551 inhibited the proliferation and migration of LUAD cells (A549 and PC9). High throughput sequencing and gene enrichment analysis revealed that LINC0551 may be involved in metabolic pathway. Glucose uptake and lactate production assays suggested that LINC00551 suppressed glycolysis of LUAD cells. Mechanistically, our work revealed that LINC00551 inhibited glycolysis in LUAD cells by impairing c-Myc-mediated transcription of an important glycolysis-related enzyme PKM2. CONCLUSION: In summary, our study identifies LINC00551 as a tumor suppressor in LUAD and implicates the LINC00551/c-Myc/PKM2 axis in the glycolytic remodeling of LUAD.