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Lack of LCAT reduces the LPS-neutralizing capacity of HDL and enhances LPS-induced inflammation in mice

Respuesta :

HDL has vital immunomodulatory properties, which includes the attenuation of lipopolysaccharide (LPS)-precipitated inflammatory reaction.

  • As lecithin-ldl cholesterol acyltransferase (LCAT) is a important enzyme withinside the maturation of HDL we investigated whether or not LCAT-deficient (Lcat(-/-)) mice gift an improved LPS-precipitated inflammatory reaction.
  • LPS (100μg/kg frame weight)-precipitated cytokine reaction in Lcat(-/-) mice become markedly improved and extended as compared to wild-kind mice. Importantly, reintroducing LCAT expression the usage of adenovirus-mediated gene switch reverted their phenotype to that of wild-kind mice. Ex vivo stimulation of complete blood with LPS (1-100ng/mL) confirmed a comparable improved pro-inflammatory phenotype.
  • Further characterization in RAW 264.7 macrophages in vitro confirmed that serum and HDL, however now no longer chylomicrons, VLDL or the lipid-unfastened protein fraction of Lcat(-/-) mice, had a discounted ability to minimize the LPS-precipitated TNFα reaction.  

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