title: Altered hepatic mRNA expression of immune response and apoptosis-associated genes after acute and chronic psychological stress in mice.
abstract: Using a combination of transcriptional profiling and Ingenuity Pathway Analysis (IPA, www.ingenuity.com) we investigated acute and chronic psychological stress induced alterations of hepatic gene expression of BALB/c mice. Already after a 2-h single stress session, up-regulation of several LPS and glucocorticoid-sensitive immune response genes and markers related to oxidative stress and apoptotic processes were observed. Support for the existence of oxidative stress was gained by measuring increased protein carbonylation, but no alterations of immune responsiveness or cell death were measured in mice after acute stress compared to the control group. When animals were repeatedly stressed during 4.5-days, we found reduced transcription of antigen presentation molecules, altered mRNA levels of immune cell signaling mediators and persisting high expression of apoptosis-related genes. These alterations were associated with a measurable immune suppression characterized by a reduced ability to clear experimental Salmonella typhimurium infection from the liver and a heightened hepatocyte apoptosis. Moreover, genes associated with anti-oxidative functions and regenerative processes were induced in the hepatic tissue of chronically stressed mice. These findings indicate that modulation of the immune response and of apoptosis-related genes is initiated already during a single acute stress exposure. However, immune suppression will only manifest in repeatedly stressed mice which additionally show induction of protective and liver regenerative genes to prevent further hepatocyte damage.
authors: Interfaculty Institute of Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Germany.
authors: Maren
authors: M
authors: Depke
authors: Leif
authors: L
authors: Steil
authors: Grazyna
authors: G
authors: Domanska
authors: Uwe
authors: U
authors: Völker
authors: Christine
authors: C
authors: Schütt
authors: Cornelia
authors: C
authors: Kiank
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D050050:Protein Carbonylation / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D012333:RNA, Messenger