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P‐glycoprotein mediates cellular host‐defense response against Listeria monocytogenes invasion in HeLa cells
Author(s) -
Lavrentyev Eduard N,
Swanson Joseph M,
Neudeck Brien L
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb109
Subject(s) - listeria monocytogenes , listeria , intracellular , biology , listeria infection , microbiology and biotechnology , hela , western blot , gentamicin protection assay , intracellular parasite , cell , bacteria , biochemistry , gene , genetics
Cellular host‐defense is a novel area of research, which may help in prevention of diseases caused by intercellular pathogens. Expression and function of intestinal P‐glycoprotein (Pgp) plays an important role in resistance to early Listeria invasion. However, the mechanism of Pgp‐related anti‐Listeria resistance is unclear and was the subject of the present study. We used HeLa cells expressing human Pgp cDNA in pRevTet‐Off vector. Cells were incubated with Listeria and the number of intercellular pathogens was counted via confocal microscopy. Cell lysates were subjected to RTQ‐PCR and Western Blot to analyze Pgp, β‐catenin and PI3Kα abundance. Our data suggests that Pgp expression does not affect the rate of the primary Listeria invasion, but rather inhibits the growth of intercellular microorganism via S100A8/S100A9 complex activation. This effect was mediated by β‐catenin phosphorylation at Ser‐552. In PgpON cells β‐catenin phosphorylation was higher and was observed 1½ h earlier than in PgpOFF cells. In PgpON cells, Listeria‐induced increase of S100A8/S100A9 expression was more prominent and appeared 2 h earlier than in PgpOFF cells. Moreover, Pgp expression diminished Listeria‐induced PI3Kα phosphorylaiton that, presumably, decreased Listeria invasion via intracellular gap‐junctions. Thus, Pgp plays an important role in cellular host‐defense against Listeria invasion.