title: Live Staphylococcus aureus and bacterial soluble factors induce different transcriptional responses in human airway cells.
abstract: To characterize the response of respiratory epithelium to infection by Staphylococcus aureus (S. aureus), human airway cells were incubated for 1 to 24 h with a supernatant of a S. aureus culture (bacterial supernatant), then profiled with a pangenomic DNA microarray. Because an upregulation of many genes was noticed around 3 h, three independent approaches were then used to characterize the host response to a 3-h contact either with bacterial supernatant or with live bacteria: 1) a DNA microarray containing 4,200 sequence-verified probes, 2) a semiquantitative RT-PCR with a set of 537 pairs of validated primers, or 3) ELISA assay of IL-8, IL-6, TNFalpha, and PGE(2). Among others, Fos, Jun, and EGR-1 were upregulated by the bacterial supernatant and by live bacteria. Increased expression of bhlhb2 and Mig-6, promoter regions which harbor HIF responding elements, was explained by an increased expression of the HIF-1alpha protein. Activation of the inducible form of cyclooxygenase, COX-2, and of the interleukins IL-1, IL-6, and IL-8, as well as of the NF-kappaB pathway, was observed preferentially in cells in contact with bacterial supernatant. Early infection was characterized by an upregulation of anti-apoptotic genes and a downregulation of pro-apoptotic genes. This correlated with a necrotic, rather than apoptotic cell death. Overall, this first global description of an airway epithelial infection by S. aureus demonstrates a larger global response to bacterial supernatant (in term of altered genes and variation factors) than to exponentially growing live bacteria.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire UMR 6097 Centre National de la Recherche Scientifique, Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: Chimène
authors.initials: C
authors.lastname: Moreilhon
authors.forename: Delphine
authors.initials: D
authors.lastname: Gras
authors.forename: Coralie
authors.initials: C
authors.lastname: Hologne
authors.forename: Odile
authors.initials: O
authors.lastname: Bajolet
authors.forename: Françoise
authors.initials: F
authors.lastname: Cottrez
authors.forename: Virginie
authors.initials: V
authors.lastname: Magnone
authors.forename: Marc
authors.initials: M
authors.lastname: Merten
authors.forename: Hervé
authors.initials: H
authors.lastname: Groux
authors.forename: Edith
authors.initials: E
authors.lastname: Puchelle
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
mesh_terms: D018929:Cell Culture Techniques; D002457:Cell Extracts / Q000494:pharmacology; D019295:Computational Biology; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000382:microbiology* / Q000502:physiology*; D013211:Staphylococcus aureus / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002457:Cell Extracts; D018076:DNA, Complementary; D012313:RNA