Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus.
(2015) In PLoS ONE 10(4).- Abstract
- Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE... (More)
- Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (p<0.0001) as compared to healthy individuals. SLE patients with ongoing type I IFN activity, as determined by an in-house reporter assay, had decreased serum levels of serotonin (p=0.0008) as well as increased IDO activity (p<0.0001), as determined by the kynurenine/tryptophan ratio measured by liquid chromatography. Furthermore, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Also platelet activation contributed to reduce overall availability of serotonin levels in platelets and serum (p<0.05). Decreased serum serotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5341082
- author
- Lood, Christian LU ; Tydén, Helena LU ; Gullstrand, Birgitta LU ; Klint, Cecilia LU ; Wenglén, Christina LU ; Nielsen, Christoffer T ; Heegaard, Niels H H ; Jönsen, Andreas LU ; Kahn, Robin LU and Bengtsson, Anders LU
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 10
- issue
- 4
- article number
- e0125109
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:25897671
- wos:000353212600096
- scopus:84928886034
- pmid:25897671
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0125109
- language
- English
- LU publication?
- yes
- id
- 4af9d34b-807d-49df-9d49-c3d34102679b (old id 5341082)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25897671?dopt=Abstract
- date added to LUP
- 2016-04-01 14:49:08
- date last changed
- 2022-04-22 05:24:53
@article{4af9d34b-807d-49df-9d49-c3d34102679b, abstract = {{Serotonin, a highly pro-inflammatory molecule released by activated platelets, is formed by tryptophan. Tryptophan is also needed in the production of kynurenine, a process mediated by the type I interferon (IFN)-regulated rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO). The aim of this study was to investigate levels of serotonin in patients with the autoimmune disease systemic lupus erythematosus (SLE), association to clinical phenotype and possible involvement of IDO in regulation of serotonin synthesis. Serotonin levels were measured in serum and plasma from patients with SLE (n=148) and healthy volunteers (n=79) by liquid chromatography and ELISA, as well as intracellularly in platelets by flow cytometry. We found that SLE patients had decreased serotonin levels in serum (p=0.01) and platelets (p<0.0001) as compared to healthy individuals. SLE patients with ongoing type I IFN activity, as determined by an in-house reporter assay, had decreased serum levels of serotonin (p=0.0008) as well as increased IDO activity (p<0.0001), as determined by the kynurenine/tryptophan ratio measured by liquid chromatography. Furthermore, SLE sera induced IDO expression in WISH cells in a type I IFN-dependent manner (p=0.008). Also platelet activation contributed to reduce overall availability of serotonin levels in platelets and serum (p<0.05). Decreased serum serotonin levels were associated with severe SLE with presence of anti-dsDNA antibodies and nephritis. In all, reduced serum serotonin levels in SLE patients were related to severe disease phenotype, including nephritis, suggesting involvement of important immunopathological processes. Further, our data suggest that type I IFNs, present in SLE sera, are able to up-regulate IDO expression, which may lead to decreased serum serotonin levels.}}, author = {{Lood, Christian and Tydén, Helena and Gullstrand, Birgitta and Klint, Cecilia and Wenglén, Christina and Nielsen, Christoffer T and Heegaard, Niels H H and Jönsen, Andreas and Kahn, Robin and Bengtsson, Anders}}, issn = {{1932-6203}}, language = {{eng}}, number = {{4}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS ONE}}, title = {{Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus.}}, url = {{https://lup.lub.lu.se/search/files/4185390/8409991}}, doi = {{10.1371/journal.pone.0125109}}, volume = {{10}}, year = {{2015}}, }