Cargando…
C-Reactive Protein Controls IL-23 Production by Human Monocytes
C-reactive protein (CRP) is an acute-phase protein in humans that is produced in high quantities by the liver upon infection and under inflammatory conditions. Although CRP is commonly used as a marker of inflammation, CRP can also directly contribute to inflammation by eliciting pro-inflammatory cy...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583945/ https://www.ncbi.nlm.nih.gov/pubmed/34769069 http://dx.doi.org/10.3390/ijms222111638 |
_version_ | 1784597326489190400 |
---|---|
author | Geyer, Chiara E. Newling, Melissa Sritharan, Lathees Griffith, Guillermo R. Chen, Hung-Jen Baeten, Dominique L. P. den Dunnen, Jeroen |
author_facet | Geyer, Chiara E. Newling, Melissa Sritharan, Lathees Griffith, Guillermo R. Chen, Hung-Jen Baeten, Dominique L. P. den Dunnen, Jeroen |
author_sort | Geyer, Chiara E. |
collection | PubMed |
description | C-reactive protein (CRP) is an acute-phase protein in humans that is produced in high quantities by the liver upon infection and under inflammatory conditions. Although CRP is commonly used as a marker of inflammation, CRP can also directly contribute to inflammation by eliciting pro-inflammatory cytokine production by immune cells. Since CRP is highly elevated in serum under inflammatory conditions, we have studied the CRP-induced cytokine profile of human monocytes, one of the main innate immune cell populations in blood. We identified that CRP is relatively unique in its capacity to induce production of the pro-inflammatory cytokine IL-23, which was in stark contrast to a wide panel of pattern recognition receptor (PRR) ligands. We show that CRP-induced IL-23 production was mediated at the level of gene transcription, since CRP particularly promoted gene transcription of IL23A (encoding IL-23p19) instead of IL12A (encoding IL-12p35), while PRR ligands induce the opposite response. Interestingly, when CRP stimulation was combined with PRR ligand stimulation, as for example, occurs in the context of sepsis, IL-23 production by monocytes was strongly reduced. Combined, these data identify CRP as a unique individual ligand to induce IL-23 production by monocytes, which may contribute to shaping systemic immune responses under inflammatory conditions. |
format | Online Article Text |
id | pubmed-8583945 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85839452021-11-12 C-Reactive Protein Controls IL-23 Production by Human Monocytes Geyer, Chiara E. Newling, Melissa Sritharan, Lathees Griffith, Guillermo R. Chen, Hung-Jen Baeten, Dominique L. P. den Dunnen, Jeroen Int J Mol Sci Article C-reactive protein (CRP) is an acute-phase protein in humans that is produced in high quantities by the liver upon infection and under inflammatory conditions. Although CRP is commonly used as a marker of inflammation, CRP can also directly contribute to inflammation by eliciting pro-inflammatory cytokine production by immune cells. Since CRP is highly elevated in serum under inflammatory conditions, we have studied the CRP-induced cytokine profile of human monocytes, one of the main innate immune cell populations in blood. We identified that CRP is relatively unique in its capacity to induce production of the pro-inflammatory cytokine IL-23, which was in stark contrast to a wide panel of pattern recognition receptor (PRR) ligands. We show that CRP-induced IL-23 production was mediated at the level of gene transcription, since CRP particularly promoted gene transcription of IL23A (encoding IL-23p19) instead of IL12A (encoding IL-12p35), while PRR ligands induce the opposite response. Interestingly, when CRP stimulation was combined with PRR ligand stimulation, as for example, occurs in the context of sepsis, IL-23 production by monocytes was strongly reduced. Combined, these data identify CRP as a unique individual ligand to induce IL-23 production by monocytes, which may contribute to shaping systemic immune responses under inflammatory conditions. MDPI 2021-10-28 /pmc/articles/PMC8583945/ /pubmed/34769069 http://dx.doi.org/10.3390/ijms222111638 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Geyer, Chiara E. Newling, Melissa Sritharan, Lathees Griffith, Guillermo R. Chen, Hung-Jen Baeten, Dominique L. P. den Dunnen, Jeroen C-Reactive Protein Controls IL-23 Production by Human Monocytes |
title | C-Reactive Protein Controls IL-23 Production by Human Monocytes |
title_full | C-Reactive Protein Controls IL-23 Production by Human Monocytes |
title_fullStr | C-Reactive Protein Controls IL-23 Production by Human Monocytes |
title_full_unstemmed | C-Reactive Protein Controls IL-23 Production by Human Monocytes |
title_short | C-Reactive Protein Controls IL-23 Production by Human Monocytes |
title_sort | c-reactive protein controls il-23 production by human monocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583945/ https://www.ncbi.nlm.nih.gov/pubmed/34769069 http://dx.doi.org/10.3390/ijms222111638 |
work_keys_str_mv | AT geyerchiarae creactiveproteincontrolsil23productionbyhumanmonocytes AT newlingmelissa creactiveproteincontrolsil23productionbyhumanmonocytes AT sritharanlathees creactiveproteincontrolsil23productionbyhumanmonocytes AT griffithguillermor creactiveproteincontrolsil23productionbyhumanmonocytes AT chenhungjen creactiveproteincontrolsil23productionbyhumanmonocytes AT baetendominiquelp creactiveproteincontrolsil23productionbyhumanmonocytes AT dendunnenjeroen creactiveproteincontrolsil23productionbyhumanmonocytes |