Retinoic acid inhibits the infectivity and growth of Chlamydia pneumoniae in epithelial and endothelial cells through different receptors

Abstract

Chlamydia pneumoniae is a human respiratory pathogen that has also been associated with cardiovascular disease. C. pneumoniae infection accelerates atherosclerotic plaque development in hyperlipidemic animals and promotes oxidation of low density lipoprotein in vitro. All-trans-retinoic acid (ATRA), an anti-oxidant, has been shown to inhibit C. pneumoniae infectivity for endothelial cells by preventing binding of the organism to the M6P/IGF-2 receptor on the cell surface. This current study investigates whether ATRA similarly affects C. pneumoniae infectivity of epithelial cells, which are the primary site of infection in the respiratory tract, and the affects on intracellular growth in both endothelial and epithelial cells. Because ATRA binds to both the nuclear RA receptor (RAR) and the M6P/IGF-2 receptor, TTNPB, an ATRA analog, which binds to the RAR but not the M6P/IGF-2 receptor was used to differentiate the receptor mediating the effects of ATRA. The results of this study showed two separate effects of ATRA. The first effect is through interaction with the M6P/IGF-2 receptor on the cell surface preventing attachment of the organism (inhibition by ATRA but not TTNPB) in endothelial cells and the second is through the nuclear receptor (inhibition by both ATRA and TTNPB) which inhibits growth in both epithelial and endothelial cells.

Retinoic acid prevents Chlamydia pneumoniae-induced foam cell development in a mouse model of atherosclerosis

“…These findings are supported by in vitro experiments demonstrating that retinoic acid inhibits attachment of C. pneumoniae to host cells and intracellular growth and these actions are mediated through different receptors. As mentioned previously retinoic acid binds to the M6P/IGF-2 receptor and inhibits attachment and infectivity of C. pneumoniae in endothelial cells [6,7]. Similarly, other pathogens including herpes simplex virus [17] and varicella-zoster virus [18] have been reported to bind to M6P/IGF-2 receptors and the infectivity of these pathogens can be inhibited by ligands of the receptor.…”

“…Cleavage of the glycan from the surface of C. pneumoniae organisms decreased infectivity of chlamydiae in cell culture [4] and mouse models of lung infection [5]. We further demonstrated that C. pneumoniae , but not C. trachomatis , binds to the mannose 6-phosphate/insulin-like growth factor-2 (M6P/IGF-2) receptor in endothelial cells, based on the finding that mannose 6-phosphate and retinoic acid, which bind to different sites on the receptor, inhibited attachment and infectivity of C. pneumoniae [6,7]. These findings suggest that the terminal mannose of the mannose oligosaccharide is phosphorylated [6].…”

Development of a Terbium Complex-Based Luminescent Probe for Imaging Endogenous Hydrogen Peroxide Generation in Plant Tissues

“…Oligosaccharide, a kind of polymer consisting of 2–10 molecules of monosaccharide linked by glucosidic bonds, has attracted much attention because it not only is water-soluble, nontoxic, and biocompatible but also possesses versatile functional properties, such as antimicrobial, anticancer, antioxidant, and immunostimulant effects. − Unfortunately, the disease resistance mechanisms of oligosaccharide in the plant system has remained unclear until now. Recent studies on the interaction between oligosaccharide and plant cells by fluorescence microscopy suggested that oligosaccharide could induce the plant cells to generate NO and H 2 O 2 , ,, which was involved in a diverse range of plant signal transduction processes and acted as a trigger signaling of plant responses against pathogens.…”

The Fox and the Rabbits—Environmental Variables and Population Genetics (1) Replication Problems in Association Studies and the Untapped Power of GWAS (2) Vitamin A Deficiency, Herpes Simplex Reactivation and Other Causes of Alzheimer's Disease

“…The vitamin A derivative, retinoic acid, inhibits herpes simplex replication [ 301 , 302 ] as well as chlamydial infection and growth [ 303 ]. Vitamin A also stunts the growth of Helicobacter pylori [ 304 ].…”