The direct communication between our central nervous and inflammatory signalling systems is a well-recognised, yet poorly understood relationship. To increase our understanding of this relationship, we examined the metabolism of serotonin and its precursor tryptophan in macrophages under inflammatory settings. Both are involved in inflammatory signalling and known to play a major role in mood regulation. Tryptophan depletion by macrophages during inflammation can consequently result in a reduction of serotonin systemically and has been suggested to cause depression. Increased understanding of this system could help overcome the problem of treatment resistant depressed patients. To this end, we treated primary human monocyte derived macrophages with a range of anti-depressant/anti-inflammatory drugs and analysed their transcriptional profile under various inflammatory conditions. In addition to the classic endotoxic driver of inflammation, LPS, we also used IFN which is a constitutive cytokine shown to directly induce depression when administered in high doses. The anti-depressant drugs were not found to have any significant effects on macrophage inflammatory signalling. However, the anti-inflammatories drugs were found to alter components of the serotonin/tryptophan metabolism pathways. This study increases our understanding of the intricacies of immune/mood cross-talk and offers into developing anti-inflammatories as co-treatment for depression.
Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages.
Sex, Specimen part, Treatment, Subject
View SamplesThis study investigated gene expression changes in whole blood samples obtained from donors diagnosed with major depressive disorder (MDD) compared to healthy controls. Micro-array data were available from whole blood on patients with MDD (N=128, 64 with generalised anxiety disorder, diagnosed by the MINI questionnaire, and 64 without anxiety disorder) and healthy controls (N=64). RNA was isolated from all samples using the standard PAXgene protocol on the Qiagen Biorobot 8000. All samples gave good quality RNA, as assessed by Agilent Bioanalyser. The yield range was 0.86-15.05ug with an average of 6.25ug. Samples were then randomised into batches, with each batch containing a representative number of controls, depression with anxiety and depression without anxiety, and the same ratio of females to males (3:1). 50ng of RNA from each sample was converted to a biotin labeled cDNA probe using NuGEN SPIA amplification. The probes were then hybridized to Affymetrix U133_Plus2.0 Genechips.
Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder.
Sex, Age, Specimen part
View SamplesGene-expression microarray datasets generated as part of the Immunological Genome Project (ImmGen). Primary cells from multiple immune lineages are isolated ex-vivo, primarily from young adult B6 male mice, and double-sorted to >99% purity. RNA is extracted from cells in a centralized manner, amplified and hybridized to Affymetrix 1.0 ST MuGene arrays. Protocols are rigorously standardized for all sorting and RNA preparation. Data is released monthly in batches of cell populations.
Transcriptomes of the B and T lineages compared by multiplatform microarray profiling.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age, Specimen part, Treatment, Time
View SamplesWe analyze the expression profile of ISGs in the context of IFNAR1-KO primary murine B cells and macrophages. These analses were used to define ISG gene sets that are under tonic control. Furthermore, these analyses enabled the definition of ISGs that are dependent on Tyk2 signaling.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age
View SamplesWe report cell specific responses to IFNg in 11 different peripheral immunocyte populations in the mouse. These cells represent the core ImmGen immunocyte lineage panel. Profiles from these were used to analyze cell specific responses to IFNg. In general a core set of ISG transcripts are induced in all cells. Smaller sets of ISGs were induced in a cell specific manner. In particular, splenic granulocytes and dendritic cells show restriced indcution of sets of ISGs.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age
View SamplesB cells respond robustly to IFNa. Here we analyze gene expression profiles of primary murine splenic B cells treated with 10 fold serially diluted IFNa in vitro. We explore sensitivity to ISGs to IFNa as they relate to dose. Generally ISGs do not cluster significantly in a dose dependent manner. However there are notable spreads in sensitivity to IFNa.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age
View SamplesWe seeked to determine in vivo effects of IFNg and IFNa response in peritoneal cavity macrophages. These cells were part of ImmGen Interferon cytokine study and immunocytes were sorted according to Immgen's standard lineage panel. Profiles from peritoneal cavity macrophages were used to analyze cell specific responses to IFNg.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age, Specimen part, Treatment
View SamplesWe describe finely resolved kinetics of the transcriptional response to IFNa in B cells in vivo. Temporal changes in expression of the most robustly induced ISGs were analyzed across 23 (15min - 15hrs) timepoints. Most ISGs reach peak induction at approximately 2hrs and generally in a synchronus manner. These analses provide insight into the regulatory network structure of IFN responses.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age
View SamplesWe report cell specific responses to IFNa in 11 different peripheral immunocyte populations in the mouse. These cells represent the core ImmGen immunocyte lineage panel. Profiles from these were used to analyze cell specific responses to IFNa. In general a core set of ISG transcripts are induced in all cells. Smaller sets of ISGs were induced in a cell specific manner. In particular, splenic granulocytes and dendritic cells show restriced indcution of sets of ISGs.
Parsing the Interferon Transcriptional Network and Its Disease Associations.
Sex, Age
View Samples