A. A. Azenabor, G. Job, S. Yang
Induction of lipoprotein lipase gene expression in Chlamydia pneumoniae-infected macrophages is dependent on Ca2+ signaling events
Unregulated uptake of low density lipoprotein (LDL) in
macrophages is the hallmark of early atherogenic lesions,
and Chlamydia pneumoniae infection of macrophages
induces this process by an unknown mechanism. It was
therefore aimed in this study to investigate (i) the role of
C. pneumoniae in macrophage expression of the lipoprotein
lipase (LpL) gene, (ii) the probable role of Ca[2+] influx
signals and (iii) the effect of the process on LDL uptake.
Lipoprotein lipase mRNA expression and LpL activity in
infected RAW-264.7 cells were significantly upregulated.
A biphasic Ca[2+] influx signal was observed in infected
cells with a moderate influx (303 nM Ca[2+]) favoring optimal
LpL gene expression. Also, the antagonists of Ltype
Ca[2+] channel in macrophages significantly downregulated
LpL gene expression and the biomolecular content
of C. pneumoniae responsible for the observed events
was in part found to be Chlamydia lipopolysaccharide
(cLPS). Investigations aimed at determining the specific
relevance of Ca[2+]dependent lipoprotein lipase gene
expression in C. pneumoniae-infected macrophages
showed that the condition caused enhanced uptake of
LDL which was abrogated by Calphostin-C-mediated
downregulation of LpL. This discovery of a specialized
Ca[2+] influx signal-mediated LpL upregulation in C. pneumoniae-infected macrophages provides a mechanistic
insight into early events involving C. pneumoniae in macrophage
foam cell formation resulting from LDL uptake.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 385, 02/2004
Pages: 67 - 74
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