title: Transcriptional control of monocyte gene expression in post-traumatic stress disorder.
abstract: Post-traumatic stress disorder (PTSD) confers an increased risk for disorders with an inflammatory etiology. PTSD-related dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis and associated alterations in inflammatory activity may contribute to this increased risk. However, little is known about convergent SNS, HPA and inflammatory signaling at the level of the immune cell transcriptome in PTSD. To explore such signaling, we examined the prevalence of specific transcription factor binding motifs in the promoter regions of differentially expressed genes in monocytes from individuals with PTSD and matched controls. Participants included 49 men (24 PTSD+ and 25 trauma-exposed controls) and 18 women (10 PTSD+ and 8 controls). Men with PTSD showed up-regulation of target genes for the NF-κB/Rel family of transcription factors, which convey inflammatory signals, up-regulation of target genes for CREB/ATF transcription factors, which convey adrenergic signals from the SNS, and down-regulation of target genes for the glucocorticoid receptor, which conveys glucocorticoid signals from the HPA axis. Women with PTSD also showed significant up-regulation of target genes for NF-κB and non-significant down-regulation of target genes for GR, but significant down-regulation of target genes for CREB/ATF. Altered transcriptional control of monocyte gene expression could contribute to exaggerated inflammatory activity in PTSD.
authors.affiliation: Veteran's Affairs Medical Center, San Francisco, CA 94121, USA. aoife.odonovan@ucsf.edu
authors.forename: Aoife
authors.initials: A
authors.lastname: O'Donovan
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
authors.forename: Steve
authors.initials: S
authors.lastname: Cole
authors.forename: Hans
authors.initials: H
authors.lastname: Rempel
authors.forename: Maryann
authors.initials: M
authors.lastname: Lenoci
authors.forename: Lynn
authors.initials: L
authors.lastname: Pulliam
authors.forename: Thomas
authors.initials: T
authors.lastname: Neylan
mesh_terms: D051697:Activating Transcription Factor 1 / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: C531110:ATF1 protein, human; D051697:Activating Transcription Factor 1; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D005819:Genetic Markers; D020569:Proto-Oncogene Proteins c-rel; D011965:Receptors, Glucocorticoid; D051996:Transcription Factor RelA