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Regulation of the i...
Regulation of the interferon-alpha production induced by RNA-containing immune complexes in plasmacytoid dendritic cells
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- Eloranta, Maija-Leena (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Systemic Autoimmunity
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- Lövgren, Tanja (författare)
- Uppsala universitet
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- Finke, Doreen (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Systemic Autoimmunity
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- Mathsson, Linda (författare)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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- Rönnelid, Johan (författare)
- Uppsala universitet,Enheten för klinisk immunologi
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Kastner, Berthold (författare)
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- Alm, Gunnar (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health
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- Rönnblom, Lars (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Systemic Autoimmunity
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(creator_code:org_t)
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- Wiley, 2009
- 2009
- Engelska.
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:8, s. 2418-2427
- Relaterad länk:
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https://onlinelibrar...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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Abstract
Ämnesord
Stäng
- OBJECTIVE: Interferon-alpha (IFNalpha) is produced in several autoimmune diseases, including systemic lupus erythematosus (SLE), and may be important in their pathogenesis. We undertook this study to investigate how IFNalpha production induced by RNA-containing immune complexes (ICs) in plasmacytoid dendritic cells (PDCs) is regulated. METHODS: Normal PDCs purified from peripheral blood mononuclear cells (PBMCs) were cocultivated with other cell populations isolated from healthy individuals or SLE patients. IFNalpha production was induced by RNA-containing ICs, which consisted of anti-RNP autoantibodies and U1 small nuclear RNP particles, and the effects of prostaglandin E2 (PGE2), reactive oxygen species (ROS), or the cytokines IFNalpha2b, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), or tumor necrosis factor alpha (TNFalpha) were explored. RESULTS: Monocytes inhibited IFNalpha production by PDCs in PBMC cultures, while natural killer (NK) cells were stimulatory. The monocytes had little effect on IFNalpha production by pure PDCs but inhibited its stimulation by NK cells. Monocytes from SLE patients were less inhibitory. Exposure of PBMCs or PDCs to IFNalpha2b/GM-CSF increased their IFNalpha production. RNA-containing ICs caused production of ROS, PGE2, and TNFalpha, especially in monocytes. These mediators and IL-10 suppressed IFNalpha production in PBMC cultures, with ROS and PGE2 also inhibiting IFNalpha production by purified PDCs. Inhibition by all of these agents, except for ROS, was abolished by IFNalpha2b/GM-CSF. The inhibitory effect of monocytes was significantly counteracted by the ROS scavengers serotonin and catalase. CONCLUSION: IFNalpha production induced by RNA-containing ICs in PDCs is regulated by a network of interactions between monocytes, NK cells, and PDCs, involving several pro- and antiinflammatory molecules. This should be considered when designing and applying new therapies.
Ämnesord
- LANTBRUKSVETENSKAPER -- Veterinärmedicin (hsv//swe)
- AGRICULTURAL SCIENCES -- Veterinary Science (hsv//eng)
- LANTBRUKSVETENSKAPER -- Husdjursvetenskap (hsv//swe)
- AGRICULTURAL SCIENCES -- Animal and Dairy Sience (hsv//eng)
Nyckelord
- interferon
- plasmacytoid dendritic cells
- NK
- monocytes
- lupus
- MEDICINE
- MEDICIN
- Immunologi
- Immunology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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