Faculty Opinions recommendation of Tumor-mediated liver X receptor-alpha activation inhibits CC chemokine receptor-7 expression on dendritic cells and dampens antitumor responses.

Gene targeting of the adaptor molecule DAP12 in mice caused abnormal distribution and impaired antigen presentation capacity of dendritic cells (DCs). However, the DAP12-associated receptors expressed on DCs and their functions have not been identified yet. Here we show that the triggering receptor expressed on myeloid cells-2 (TREM-2) is a cell surface receptor on human monocyte-derived DCs, which is associated with DAP12. TREM-2/DAP12 promotes upregulation of CC chemokine receptor 7, partial DC maturation, and DC survival through activation of protein tyrosine kinases and extracellular signal–regulated kinase. In contrast to Toll-like receptor-mediated signaling, TREM2/DAP12 stimulation is independent of nuclear factor-κB and p38 stress-activated protein kinase. This novel DC activation pathway may regulate DC homeostasis and amplify DC responses to pathogens, explaining the phenotype observed in DAP12-deficient mice.

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Faculty Opinions recommendation of A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1001054.16356 ◽

2001 ◽

Author(s):

Reina Mebius

Keyword(s):

Dendritic Cells ◽

Chemokine Receptor ◽

Cc Chemokine ◽

Human Dendritic Cells ◽

Cc Chemokine Receptor 7

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Faculty Opinions recommendation of Structural basis for allosteric ligand recognition in the human CC chemokine receptor 7.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736475238.793566005 ◽

2019 ◽

Author(s):

Xiayang Qiu ◽

Litao Sun

Keyword(s):

Chemokine Receptor ◽

Structural Basis ◽

Ligand Recognition ◽

Cc Chemokine ◽

Cc Chemokine Receptor 7

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Role of Baicalin and Liver X Receptor Alpha in the Formation of Cholesterol Gallstones in Mice

Gastroenterology Research and Practice ◽

10.1155/2020/1343969 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Geng Chen ◽

Shuodong Wu

Keyword(s):

Oxidative Stress ◽

Bile Acid ◽

Cholesterol Metabolism ◽

Density Lipoprotein ◽

Liver X Receptor ◽

Cholesterol Gallstones ◽

Receptor Alpha ◽

Lithogenic Diet ◽

Liver X Receptor Alpha ◽

And Oxidative Stress

This study was aimed at investigating the effect of baicalin on experimental cholesterol gallstones in mice. The mouse gallstone model was induced by feeding with a lithogenic diet, and cholesterol stones were found in the gallbladder. The lithogenic diet caused elevation of triglycerides, cholesterol, and low-density lipoprotein concentrations and descent of high-density lipoprotein concentration in serum. Hyperplasia and inflammatory infiltration were observed in the gallbladder wall of lithogenic diet-fed mice. We also found the increase of cholesterol content and the decrease of bile acid in bile. Real-time PCR and western blot results demonstrated that the expression levels of two enzymes (cholesterol 7α-hydroxylase (CYP7a1) and sterol 12α-hydroxylase (CYP8b1)) to catalyze the synthesis of bile acid from cholesterol were decreased and that two cholesterol transporters (ATP-binding cassette transporter G5/G8 (ABCG5/8)) were increased in the liver of lithogenic diet-fed mice. The lithogenic diet also led to enhanced activity of alanine aminotransferase and aspartate aminotransferase in serum; increased concentrations of tumor necrosis factor-α, interleukin- (IL-) 1β, IL-6, and malondialdehyde; and decreased superoxide dismutase activity in the liver, suggesting inflammatory and oxidative stress. In addition, liver X receptor alpha (LXRα) was increased in the liver. After gavage of baicalin, the lithogenic diet-induced gallstones, hyperlipidemia, gallbladder hyperplasia, inflammation, and oxidative stress in liver and cholesterol metabolism disorders were all alleviated to some degree. The expression of LXRα in the liver was inhibited by baicalin. In addition, the LXRα agonist T0901317 aggravated lithogenic diet-induced harmful symptoms in mice, including the increase of gallstone formation, hyperlipidemia, hepatic injury, inflammation, and oxidative stress. In conclusion, we demonstrated that baicalin played a protective role in a lithogenic diet-induced gallstone mouse model, which may be mediated by inhibition of LXRα activity. These findings may provide novel insights for prevention and therapy of gallstones in the clinic.

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