SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance

Cai, L., et al. 2008. J. Clin. Invest. 118, 364-375

Speaker: Juin-Wei Chen  (陳君瑋)                       Time: 13:00~14:00, Ape. 16, 2008

Commentator: 劉清泉醫師                          Place: Room 601

Abstract:

    In most situations, severe sepsis is due to bacterial lipopolysaccharide (LPS)-induced uncontrolled inflammation. To avoid of the mortal situation of sepsis, anti-inflammation treatment is necessary in clinic. Previous studies show that cholesterol uptake in adrenal glands results in glucocorticoids production which is important for inflammation suppression. Thus, the authors wanted to clarify if the HDL and LPS receptor, scavenger receptor B-I (SR-BI), which is important for cholesterol uptake participated in anti-LPS-induced sepsis. They firstly demonstrated that SR-BI helped reduce pro-inflammatory cytokines and maintained the survival rate compared with SR-BI null mice. After challenged with LPS, SR-BI null mice were obviously disabled from corticosterone synthesis under normal ACTH release, and suppression of pro-inflammatory cytokines. Being infected with G(-) bacteria E. coli and under stress of cold water swimming, SR-BI mice lead to strong pro-inflammatory cytokine responses and suppressive corticosterone production. Furthermore, the authors excised the adrenal glands of mice and discovered that both normal and SR-BI null mice couldn’t control increased pro-inflammatory cytokines and had less corticosterone synthesis. In SR-BI null mice, limited cholesterol availability leads to little corticosterone production, even though the relating to corticosterone biosynthesis enzymes express normally. Therefore, SR-BI is very essential for adrenal glucocorticoids production. The authors finally proved that SR-BI binding with HDL and LPS is also important for LPS clearance by liver to avoid of severe sepsis. To sum up, the anti-septic functions of SR-BI mainly participate in cholesterol transport relative to glucocorticoids production and LPS clearance.

References:

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2. Van Amersfoort, E. S., et al. 2003. Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock. Clin. Microbiol. Rev. 16, 379-414