Research Article Open Access

Inhibition of Cholesterol Esterification Influences Cytokine Exspression in Lypopolisaccharide-activated P388D1 Macrophages

Rosa Rita Bonatesta1, Francesca Sanna1, Sabrina Uda1, Bruno Frongia1, Stefano Pintus1, Paolo Pintus1, Maria Collu1, Alessandra Saddi1 and Barbara Batetta1
  • 1 University of Cagliari, Italy

Abstract

Several in vivo and in vitro studies have demonstrated the involvement of infectious agents in the development of atherosclerosis. However, the mechanisms by which micro-organisms induce and/or aggravate atherosclerosis, are so far unclear. Accumulation of cholesterol esters and lipid laden cell formation are hallmark of the atherogenesis, however, the possible relationship between cholesterol esterification and the signal-transducing component of LPS recognition complex inducing cytokine secretion has not been yet investigated. In the present study, we investigated the effect of mevinolin, the ACAT inhibitor, Sandoz 58035, and plasma from statin-treated hypercholesterolemic patients on cholesterol metabolism and cytokine expression in LPS activated P388D1 macrophages. In P388D1 macrophages cholesterol synthesis and uptake, as well as cholesterol ester synthesis, were unchanged following LPS-activation. When cells were grown in presence of serum from patients under statin therapy, cholesterol esterification was lower compared to cells grown with plasma from healthy subjects, independently from the type of statin used. This effect was accompanied by inhibition of IL-1β expression in LPS activated cells. The ACAT inhibitor, Sandoz 58035, which completely blocked cholesterol esterification in normal and LPS-activated macrophages, prevented IL-1β and IL-6 over-expression in LPS activated cells. Although preliminary, these data point to a possible relationship between cholesterol esterification and cytokine production in macrophages, prospecting new possible mechanisms by which microbial or inflammatory agents may induce and/or accelerate the atherosclerotic process.

American Journal of Infectious Diseases
Volume 3 No. 3, 2007, 151-158

DOI: https://doi.org/10.3844/ajidsp.2007.151.158

Submitted On: 12 May 2007 Published On: 30 September 2007

How to Cite: Bonatesta, R. R., Sanna, F., Uda, S., Frongia, B., Pintus, S., Pintus, P., Collu, M., Saddi, A. & Batetta, B. (2007). Inhibition of Cholesterol Esterification Influences Cytokine Exspression in Lypopolisaccharide-activated P388D1 Macrophages. American Journal of Infectious Diseases, 3(3), 151-158. https://doi.org/10.3844/ajidsp.2007.151.158

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Keywords

  • Infections
  • Atherosclerosis
  • Macrophages
  • Lypopolisaccharide
  • Cytokines
  • Cholesterol Esterification