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Publication : Hepatic scavenger receptor BI protects against polymicrobial-induced sepsis through promoting LPS clearance in mice.

First Author  Guo L Year  2014
Journal  J Biol Chem Volume  289
Issue  21 Pages  14666-73
PubMed ID  24719333 Mgi Jnum  J:214115
Mgi Id  MGI:5588076 Doi  10.1074/jbc.M113.537258
Citation  Guo L, et al. (2014) Hepatic scavenger receptor BI protects against polymicrobial-induced sepsis through promoting LPS clearance in mice. J Biol Chem 289(21):14666-73
abstractText  Recent studies revealed that scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. However, the mechanisms underlying this protection remain largely unknown. In this study, using Scarb1(I179N) mice, a mouse model specifically deficient in hepatic SR-BI, we report that hepatic SR-BI protects against cecal ligation and puncture (CLP)-induced sepsis as shown by 75% fatality in Scarb1(I179N) mice, but only 21% fatality in C57BL/6J control mice. The increase in fatality in Scarb1(I179N) mice was associated with an exacerbated inflammatory cytokine production. Further study demonstrated that hepatic SR-BI exerts its protection against sepsis through its role in promoting LPS clearance without affecting the inflammatory response in macrophages, the glucocorticoid production in adrenal glands, the leukocyte recruitment to peritoneum or the bacterial clearance in liver. Our findings reveal hepatic SR-BI as a critical protective factor in sepsis and point out that promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis.
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