title: Listeria monocytogenes activated p38 MAPK and induced IL-8 secretion in a nucleotide-binding oligomerization domain 1-dependent manner in endothelial cells.
abstract: Nucleotide-binding oligomerization domain (Nod) proteins serve as intracellular pattern recognition molecules recognizing peptidoglycans. To further examine intracellular immune recognition, we used Listeria monocytogenes as an organism particularly amenable for studying innate immunity to intracellular pathogens. In contrast to wild-type L. monocytogenes, the nonpathogenic Listeria innocua, or L. monocytogenes mutants lacking internalin B or listeriolysin O, poorly invaded host cells and escaped into host cell cytoplasm, respectively, and were therefore used as controls. In this study, we show that only the invasive wild-type L. monocytogenes, but not the listeriolysin O- or internalin B-negative L. monocytogenes mutants or L. innocua, substantially induced IL-8 production in HUVEC. RNA interference and Nod1-overexpression experiments demonstrated that Nod1 is critically involved in chemokine secretion and NF-kappaB activation initiated by L. monocytogenes in human endothelial cells. Moreover, we show for the first time that Nod1 mediated activation of p38 MAPK signaling induced by L. monocytogenes. Finally, L. monocytogenes- and Nod1-induced IL-8 production was blocked by a specific p38 inhibitor. In conclusion, L. monocytogenes induced a Nod1-dependent activation of p38 MAPK signaling and NF-kappaB which resulted in IL-8 production in endothelial cells. Thus, Nod1 is an important component of a cytoplasmic surveillance pathway.
authors.affiliation: Department of Internal Medicine/Infectious Diseases, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
authors.forename: Anja
authors.initials: A
authors.lastname: Püschel
authors.forename: Wiebke
authors.initials: W
authors.lastname: Beermann
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Hocke
authors.forename: Stefanie
authors.initials: S
authors.lastname: Förster
authors.forename: Bernd
authors.initials: B
authors.lastname: Schmeck
authors.forename: Vincent
authors.initials: V
authors.lastname: van Laak
authors.forename: Trinad
authors.initials: T
authors.lastname: Chakraborty
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.forename: Stefan
authors.initials: S
authors.lastname: Hippenstiel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology* / Q000382:microbiology*; D004789:Enzyme Activation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology*; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016209:Interleukin-8; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases