title: Infection with Leishmania infantum Inhibits actinomycin D-induced apoptosis of human monocytic cell line U-937.
abstract: Modulation of host cell apoptosis has been observed in many bacterial, protozoal, and viral infections. The aim of this work was to investigate the effect of viscerotropic Leishmania (L.) infantum infection on actinomycin D-induced apoptosis of the human monocytic cell line U-937. Cells were infected with L. infantum promastigotes or treated with the surface molecule lipophosphoglycan (LPG) or with parasite-free supernatant of Leishmania culture medium and submitted to action of actinomycin D as the apoptosis-inducing agent. Actinomycin D-induced apoptosis in U-937 cells was inhibited in the presence of both viable L. infantum promastigotes and soluble factors contained in Leishmania culture medium or purified LPG. Leishmania infantum affected the survival of U-937 cells via a mechanism involving inhibition of caspase-3 activation. Furthermore, protein kinase C delta (PKC delta) cleavage was increased in actinomycin D-treated U-937 cells and was inhibited by the addition of LPG. Thus, inhibition of the PKC-mediated pathways by LPG can be implicated in the enhanced survival of the parasites. These results support the claim that promastigotes of L. infantum, as well as its surface molecule, LPG, which is in part released in the culture medium, inhibit macrophage apoptosis, thus allowing intracellular parasite survival and replication.
authors.affiliation: Department of Human Anatomy and Histology, University of Bari, I-70124 Bari, Italy. s.lisi@anatomia.unib.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Lisi
authors.forename: Margherita
authors.initials: M
authors.lastname: Sisto
authors.forename: Angela
authors.initials: A
authors.lastname: Acquafredda
authors.forename: Rosa
authors.initials: R
authors.lastname: Spinelli
authors.forename: Mariaangela
authors.initials: M
authors.lastname: Schiavone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mitolo
authors.forename: Olga
authors.initials: O
authors.lastname: Brandonisio
authors.forename: Mariaantonietta
authors.initials: M
authors.lastname: Panaro
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D003609:Dactinomycin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018314:Leishmania infantum / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects* / Q000469:parasitology*; D010401:Penicillin G Benzathine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D020298:U937 Cells
chemical_list: D000953:Antigens, Protozoan; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D003609:Dactinomycin; D011493:Protein Kinase C; C505407:CASP3 protein, human; D053148:Caspase 3; D010401:Penicillin G Benzathine