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| Status |
Public on Jan 01, 2018 |
| Title |
Transcriptional effects of anti-inflammatory or anti-depressant drugs on primary human macrophages inflammatory response |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
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 IFNα 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.
We treated human primary macrophage cells with anti-inflammatory or anti-depressant drugs and analysed their transcriptional effects during inf.lammatory signaling within the context of tryptophan metabolism/kynurenic metabolism.
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| Overall design |
Primary human CD14+ monocytes were isolated from the whole blood of 6 donors (3 male, 3 female). These were transformed in macrophages through CSF-1 stimulation over a week. Cells were then subject to inflammatory stimulus with LPS (10 ng/ml) or IFNa (50 U/ml) for 7 or 24 h or incubated for 24 h with no inflammatory stimulus. In each of these 5 conditions, cells were treated for the same amount of time with either vehicle control (DMSO), escitalopram (SSRI antidepressant), nortriptyline (tricyclic antidepressant), anti-TNFa (neutralising antibody anti-inflammatory), indomethacin (non-steroidal anti-inflammatory), prednisolone (steroidal anti-inflammatory) or left untreated.
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| Contributor(s) |
Regan T, Freeman T |
| Citation(s) |
29377288 |
| Submission date |
Aug 08, 2016 |
| Last update date |
Apr 02, 2018 |
| Contact name |
Tim Regan |
| E-mail(s) |
tim.regan@roslin.ed.ac.uk
|
| Phone |
00441316519205
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| Organization name |
The Roslin Institute, University of Edinburgh
|
| Department |
Genetics and genomics
|
| Lab |
Prof. Freeman
|
| Street address |
Easter Bush Campus
|
| City |
Midlothian |
| ZIP/Postal code |
EH25 9RG |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL22299 |
[HuGene-2_1-st] Affymetrix Human Gene 2.1 ST Array [gene name version] |
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| Samples (185)
|
| GSM2264869 |
Macrophage cell, D1 Female, 24 h Untreated, 1 Untreated |
| GSM2264870 |
Macrophage cell, D1 Female, 24 h Untreated, 2 CTRL |
| GSM2264871 |
Macrophage cell, D1 Female, 24 h Untreated, 3 Escitalopram |
| GSM2264872 |
Macrophage cell, D1 Female, 24 h Untreated, 4 Nortriptyline |
| GSM2264873 |
Macrophage cell, D1 Female, 24 h Untreated, 5 Anti-TNFa |
| GSM2264874 |
Macrophage cell, D1 Female, 24 h Untreated, 6 Indomethacin |
| GSM2264875 |
Macrophage cell, D1 Female, 24 h Untreated, 7 Prednisolone |
| GSM2264876 |
Macrophage cell, D1 Female, IFN 07 h, 1 Untreated |
| GSM2264877 |
Macrophage cell, D1 Female, IFN 07 h, 2 CTRL |
| GSM2264878 |
Macrophage cell, D1 Female, IFN 07 h, 3 Escitalopram |
| GSM2264879 |
Macrophage cell, D1 Female, IFN 07 h, 4 Nortriptyline |
| GSM2264880 |
Macrophage cell, D1 Female, IFN 07 h, 5 Anti-TNFa |
| GSM2264881 |
Macrophage cell, D1 Female, IFN 07 h, 6 Indomethacin |
| GSM2264882 |
Macrophage cell, D1 Female, IFN 07 h, 7 Prednisolone |
| GSM2264883 |
Macrophage cell, D1 Female, IFN 24 h, 1 Untreated |
| GSM2264884 |
Macrophage cell, D1 Female, IFN 24 h, 2 CTRL |
| GSM2264885 |
Macrophage cell, D1 Female, IFN 24 h, 3 Escitalopram |
| GSM2264886 |
Macrophage cell, D1 Female, IFN 24 h, 4 Nortriptyline |
| GSM2264887 |
Macrophage cell, D1 Female, IFN 24 h, 5 Anti-TNFa |
| GSM2264888 |
Macrophage cell, D1 Female, IFN 24 h, 6 Indomethacin |
| GSM2264889 |
Macrophage cell, D1 Female, IFN 24 h, 7 Prednisolone |
| GSM2264890 |
Macrophage cell, D1 Female, LPS 07 h, 1 Untreated |
| GSM2264891 |
Macrophage cell, D1 Female, LPS 07 h, 2 CTRL |
| GSM2264892 |
Macrophage cell, D1 Female, LPS 07 h, 3 Escitalopram |
| GSM2264893 |
Macrophage cell, D1 Female, LPS 07 h, 4 Nortriptyline |
| GSM2264894 |
Macrophage cell, D1 Female, LPS 07 h, 5 Anti-TNFa |
| GSM2264895 |
Macrophage cell, D1 Female, LPS 07 h, 6 Indomethacin |
| GSM2264896 |
Macrophage cell, D1 Female, LPS 07 h, 7 Prednisolone |
| GSM2264897 |
Macrophage cell, D1 Female, LPS 24 h, 1 Untreated |
| GSM2264898 |
Macrophage cell, D1 Female, LPS 24 h, 2 CTRL |
| GSM2264899 |
Macrophage cell, D1 Female, LPS 24 h, 3 Escitalopram |
| GSM2264900 |
Macrophage cell, D1 Female, LPS 24 h, 4 Nortriptyline |
| GSM2264901 |
Macrophage cell, D1 Female, LPS 24 h, 5 Anti-TNFa |
| GSM2264902 |
Macrophage cell, D1 Female, LPS 24 h, 6 Indomethacin |
| GSM2264903 |
Macrophage cell, D1 Female, LPS 24 h, 7 Prednisolone |
| GSM2264904 |
Macrophage cell, D2 Male, 24 h Untreated, 1 Untreated |
| GSM2264905 |
Macrophage cell, D2 Male, 24 h Untreated, 2 CTRL |
| GSM2264906 |
Macrophage cell, D2 Male, 24 h Untreated, 3 Escitalopram |
| GSM2264907 |
Macrophage cell, D2 Male, 24 h Untreated, 4 Nortriptyline |
| GSM2264908 |
Macrophage cell, D2 Male, 24 h Untreated, 5 Anti-TNFa |
| GSM2264909 |
Macrophage cell, D2 Male, 24 h Untreated, 6 Indomethacin |
| GSM2264910 |
Macrophage cell, D2 Male, 24 h Untreated, 7 Prednisolone |
| GSM2264911 |
Macrophage cell, D2 Male, IFN 07 h, 1 Untreated |
| GSM2264912 |
Macrophage cell, D2 Male, IFN 07 h, 2 CTRL |
| GSM2264913 |
Macrophage cell, D2 Male, IFN 07 h, 3 Escitalopram |
| GSM2264914 |
Macrophage cell, D2 Male, IFN 07 h, 4 Nortriptyline |
| GSM2264915 |
Macrophage cell, D2 Male, IFN 07 h, 5 Anti-TNFa |
| GSM2264916 |
Macrophage cell, D2 Male, IFN 07 h, 6 Indomethacin |
| GSM2264917 |
Macrophage cell, D2 Male, IFN 07 h, 7 Prednisolone |
| GSM2264918 |
Macrophage cell, D2 Male, IFN 24 h, 1 Untreated |
| GSM2264919 |
Macrophage cell, D2 Male, IFN 24 h, 2 CTRL |
| GSM2264920 |
Macrophage cell, D2 Male, IFN 24 h, 3 Escitalopram |
| GSM2264921 |
Macrophage cell, D2 Male, IFN 24 h, 4 Nortriptyline |
| GSM2264922 |
Macrophage cell, D2 Male, IFN 24 h, 5 Anti-TNFa |
| GSM2264923 |
Macrophage cell, D2 Male, IFN 24 h, 6 Indomethacin |
| GSM2264924 |
Macrophage cell, D2 Male, IFN 24 h, 7 Prednisolone |
| GSM2264925 |
Macrophage cell, D2 Male, LPS 07 h, 1 Untreated |
| GSM2264926 |
Macrophage cell, D2 Male, LPS 07 h, 2 CTRL |
| GSM2264927 |
Macrophage cell, D2 Male, LPS 07 h, 3 Escitalopram |
| GSM2264928 |
Macrophage cell, D2 Male, LPS 07 h, 4 Nortriptyline |
| GSM2264929 |
Macrophage cell, D2 Male, LPS 07 h, 5 Anti-TNFa |
| GSM2264930 |
Macrophage cell, D2 Male, LPS 07 h, 7 Prednisolone |
| GSM2264931 |
Macrophage cell, D2 Male, LPS 24 h, 1 Untreated |
| GSM2264932 |
Macrophage cell, D2 Male, LPS 24 h, 2 CTRL |
| GSM2264933 |
Macrophage cell, D2 Male, LPS 24 h, 3 Escitalopram |
| GSM2264934 |
Macrophage cell, D2 Male, LPS 24 h, 4 Nortriptyline |
| GSM2264935 |
Macrophage cell, D2 Male, LPS 24 h, 5 Anti-TNFa |
| GSM2264936 |
Macrophage cell, D2 Male, LPS 24 h, 6 Indomethacin |
| GSM2264937 |
Macrophage cell, D2 Male, LPS 24 h, 7 Prednisolone |
| GSM2264938 |
Macrophage cell, D3 Female, 24 h Untreated, 1 Untreated |
| GSM2264939 |
Macrophage cell, D3 Female, 24 h Untreated, 2 CTRL |
| GSM2264940 |
Macrophage cell, D3 Female, 24 h Untreated, 3 Escitalopram |
| GSM2264941 |
Macrophage cell, D3 Female, 24 h Untreated, 4 Nortriptyline |
| GSM2264942 |
Macrophage cell, D3 Female, 24 h Untreated, 5 Anti-TNFa |
| GSM2264943 |
Macrophage cell, D3 Female, 24 h Untreated, 6 Indomethacin |
| GSM2264944 |
Macrophage cell, D3 Female, 24 h Untreated, 7 Prednisolone |
| GSM2264945 |
Macrophage cell, D3 Female, IFN 07 h, 1 Untreated |
| GSM2264946 |
Macrophage cell, D3 Female, IFN 07 h, 3 Escitalopram |
| GSM2264947 |
Macrophage cell, D3 Female, IFN 07 h, 4 Nortriptyline |
| GSM2264948 |
Macrophage cell, D3 Female, IFN 07 h, 5 Anti-TNFa |
| GSM2264949 |
Macrophage cell, D3 Female, IFN 07 h, 7 Prednisolone |
| GSM2264950 |
Macrophage cell, D3 Female, IFN 24 h, 1 Untreated |
| GSM2264951 |
Macrophage cell, D3 Female, IFN 24 h, 2 CTRL |
| GSM2264952 |
Macrophage cell, D3 Female, IFN 24 h, 3 Escitalopram |
| GSM2264953 |
Macrophage cell, D3 Female, IFN 24 h, 4 Nortriptyline |
| GSM2264954 |
Macrophage cell, D3 Female, IFN 24 h, 5 Anti-TNFa |
| GSM2264955 |
Macrophage cell, D3 Female, IFN 24 h, 6 Indomethacin |
| GSM2264956 |
Macrophage cell, D3 Female, IFN 24 h, 7 Prednisolone |
| GSM2264957 |
Macrophage cell, D3 Female, LPS 07 h, 1 Untreated |
| GSM2264958 |
Macrophage cell, D3 Female, LPS 07 h, 2 CTRL |
| GSM2264959 |
Macrophage cell, D3 Female, LPS 07 h, 3 Escitalopram |
| GSM2264960 |
Macrophage cell, D3 Female, LPS 07 h, 4 Nortriptyline |
| GSM2264961 |
Macrophage cell, D3 Female, LPS 07 h, 5 Anti-TNFa |
| GSM2264962 |
Macrophage cell, D3 Female, LPS 07 h, 6 Indomethacin |
| GSM2264963 |
Macrophage cell, D3 Female, LPS 07 h, 7 Prednisolone |
| GSM2264964 |
Macrophage cell, D3 Female, LPS 24 h, 1 Untreated |
| GSM2264965 |
Macrophage cell, D3 Female, LPS 24 h, 2 CTRL |
| GSM2264966 |
Macrophage cell, D3 Female, LPS 24 h, 3 Escitalopram |
| GSM2264967 |
Macrophage cell, D3 Female, LPS 24 h, 5 Anti-TNFa |
| GSM2264968 |
Macrophage cell, D3 Female, LPS 24 h, 7 Prednisolone |
| GSM2264969 |
Macrophage cell, D4 Male, 24 h Untreated, 1 Untreated |
| GSM2264970 |
Macrophage cell, D4 Male, 24 h Untreated, 2 CTRL |
| GSM2264971 |
Macrophage cell, D4 Male, 24 h Untreated, 3 Escitalopram |
| GSM2264972 |
Macrophage cell, D4 Male, 24 h Untreated, 4 Nortriptyline |
| GSM2264973 |
Macrophage cell, D4 Male, 24 h Untreated, 5 Anti-TNFa |
| GSM2264974 |
Macrophage cell, D4 Male, 24 h Untreated, 6 Indomethacin |
| GSM2264975 |
Macrophage cell, D4 Male, 24 h Untreated, 7 Prednisolone |
| GSM2264976 |
Macrophage cell, D4 Male, IFN 07 h, 1 Untreated |
| GSM2264977 |
Macrophage cell, D4 Male, IFN 07 h, 2 CTRL |
| GSM2264978 |
Macrophage cell, D4 Male, IFN 07 h, 3 Escitalopram |
| GSM2264979 |
Macrophage cell, D4 Male, IFN 07 h, 4 Nortriptyline |
| GSM2264980 |
Macrophage cell, D4 Male, IFN 07 h, 5 Anti-TNFa |
| GSM2264981 |
Macrophage cell, D4 Male, IFN 07 h, 6 Indomethacin |
| GSM2264982 |
Macrophage cell, D4 Male, IFN 07 h, 7 Prednisolone |
| GSM2264983 |
Macrophage cell, D4 Male, IFN 24 h, 1 Untreated |
| GSM2264984 |
Macrophage cell, D4 Male, IFN 24 h, 2 CTRL |
| GSM2264985 |
Macrophage cell, D4 Male, IFN 24 h, 3 Escitalopram |
| GSM2264986 |
Macrophage cell, D4 Male, IFN 24 h, 4 Nortriptyline |
| GSM2264987 |
Macrophage cell, D4 Male, IFN 24 h, 5 Anti-TNFa |
| GSM2264988 |
Macrophage cell, D4 Male, IFN 24 h, 6 Indomethacin |
| GSM2264989 |
Macrophage cell, D4 Male, IFN 24 h, 7 Prednisolone |
| GSM2264990 |
Macrophage cell, D4 Male, LPS 07 h, 1 Untreated |
| GSM2264991 |
Macrophage cell, D4 Male, LPS 07 h, 2 CTRL |
| GSM2264992 |
Macrophage cell, D4 Male, LPS 07 h, 3 Escitalopram |
| GSM2264993 |
Macrophage cell, D4 Male, LPS 07 h, 4 Nortriptyline |
| GSM2264994 |
Macrophage cell, D4 Male, LPS 07 h, 5 Anti-TNFa |
| GSM2264995 |
Macrophage cell, D4 Male, LPS 07 h, 6 Indomethacin |
| GSM2264996 |
Macrophage cell, D4 Male, LPS 07 h, 7 Prednisolone |
| GSM2264997 |
Macrophage cell, D4 Male, LPS 24 h, 1 Untreated |
| GSM2264998 |
Macrophage cell, D4 Male, LPS 24 h, 2 CTRL |
| GSM2264999 |
Macrophage cell, D4 Male, LPS 24 h, 3 Escitalopram |
| GSM2265000 |
Macrophage cell, D4 Male, LPS 24 h, 4 Nortriptyline |
| GSM2265001 |
Macrophage cell, D4 Male, LPS 24 h, 5 Anti-TNFa |
| GSM2265002 |
Macrophage cell, D4 Male, LPS 24 h, 6 Indomethacin |
| GSM2265003 |
Macrophage cell, D4 Male, LPS 24 h, 7 Prednisolone |
| GSM2265004 |
Macrophage cell, D5 Female, 24 h Untreated, 1 Untreated |
| GSM2265005 |
Macrophage cell, D5 Female, 24 h Untreated, 2 CTRL |
| GSM2265006 |
Macrophage cell, D5 Female, 24 h Untreated, 5 Anti-TNFa |
| GSM2265007 |
Macrophage cell, D5 Female, 24 h Untreated, 6 Indomethacin |
| GSM2265008 |
Macrophage cell, D5 Female, 24 h Untreated, 7 Prednisolone |
| GSM2265009 |
Macrophage cell, D5 Female, IFN 07 h, 1 Untreated |
| GSM2265010 |
Macrophage cell, D5 Female, IFN 07 h, 2 CTRL |
| GSM2265011 |
Macrophage cell, D5 Female, IFN 07 h, 5 Anti-TNFa |
| GSM2265012 |
Macrophage cell, D5 Female, IFN 07 h, 6 Indomethacin |
| GSM2265013 |
Macrophage cell, D5 Female, IFN 07 h, 7 Prednisolone |
| GSM2265014 |
Macrophage cell, D5 Female, IFN 24 h, 1 Untreated |
| GSM2265015 |
Macrophage cell, D5 Female, IFN 24 h, 2 CTRL |
| GSM2265016 |
Macrophage cell, D5 Female, IFN 24 h, 5 Anti-TNFa |
| GSM2265017 |
Macrophage cell, D5 Female, IFN 24 h, 6 Indomethacin |
| GSM2265018 |
Macrophage cell, D5 Female, IFN 24 h, 7 Prednisolone |
| GSM2265019 |
Macrophage cell, D5 Female, LPS 07 h, 1 Untreated |
| GSM2265020 |
Macrophage cell, D5 Female, LPS 07 h, 2 CTRL |
| GSM2265021 |
Macrophage cell, D5 Female, LPS 07 h, 5 Anti-TNFa |
| GSM2265022 |
Macrophage cell, D5 Female, LPS 07 h, 6 Indomethacin |
| GSM2265023 |
Macrophage cell, D5 Female, LPS 07 h, 7 Prednisolone |
| GSM2265024 |
Macrophage cell, D5 Female, LPS 24 h, 1 Untreated |
| GSM2265025 |
Macrophage cell, D5 Female, LPS 24 h, 2 CTRL |
| GSM2265026 |
Macrophage cell, D5 Female, LPS 24 h, 5 Anti-TNFa |
| GSM2265027 |
Macrophage cell, D5 Female, LPS 24 h, 6 Indomethacin |
| GSM2265028 |
Macrophage cell, D5 Female, LPS 24 h, 7 Prednisolone |
| GSM2265029 |
Macrophage cell, D6 Male, 24 h Untreated, 1 Untreated |
| GSM2265030 |
Macrophage cell, D6 Male, 24 h Untreated, 2 CTRL |
| GSM2265031 |
Macrophage cell, D6 Male, 24 h Untreated, 5 Anti-TNFa |
| GSM2265032 |
Macrophage cell, D6 Male, 24 h Untreated, 6 Indomethacin |
| GSM2265033 |
Macrophage cell, D6 Male, 24 h Untreated, 7 Prednisolone |
| GSM2265034 |
Macrophage cell, D6 Male, IFN 07 h, 1 Untreated |
| GSM2265035 |
Macrophage cell, D6 Male, IFN 07 h, 2 CTRL |
| GSM2265036 |
Macrophage cell, D6 Male, IFN 07 h, 5 Anti-TNFa |
| GSM2265037 |
Macrophage cell, D6 Male, IFN 07 h, 6 Indomethacin |
| GSM2265038 |
Macrophage cell, D6 Male, IFN 07 h, 7 Prednisolone |
| GSM2265039 |
Macrophage cell, D6 Male, IFN 24 h, 1 Untreated |
| GSM2265040 |
Macrophage cell, D6 Male, IFN 24 h, 2 CTRL |
| GSM2265041 |
Macrophage cell, D6 Male, IFN 24 h, 5 Anti-TNFa |
| GSM2265042 |
Macrophage cell, D6 Male, IFN 24 h, 6 Indomethacin |
| GSM2265043 |
Macrophage cell, D6 Male, IFN 24 h, 7 Prednisolone |
| GSM2265044 |
Macrophage cell, D6 Male, LPS 07 h, 1 Untreated |
| GSM2265045 |
Macrophage cell, D6 Male, LPS 07 h, 2 CTRL |
| GSM2265046 |
Macrophage cell, D6 Male, LPS 07 h, 5 Anti-TNFa |
| GSM2265047 |
Macrophage cell, D6 Male, LPS 07 h, 6 Indomethacin |
| GSM2265048 |
Macrophage cell, D6 Male, LPS 07 h, 7 Prednisolone |
| GSM2265049 |
Macrophage cell, D6 Male, LPS 24 h, 1 Untreated |
| GSM2265050 |
Macrophage cell, D6 Male, LPS 24 h, 2 CTRL |
| GSM2265051 |
Macrophage cell, D6 Male, LPS 24 h, 5 Anti-TNFa |
| GSM2265052 |
Macrophage cell, D6 Male, LPS 24 h, 6 Indomethacin |
| GSM2265053 |
Macrophage cell, D6 Male, LPS 24 h, 7 Prednisolone |
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| Relations |
| BioProject |
PRJNA338182 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE85333_RAW.tar |
860.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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