Journal
AUTOIMMUNITY
Volume 45, Issue 8, Pages 602-611Publisher
INFORMA HEALTHCARE
DOI: 10.3109/08916934.2012.719948
Keywords
Pristane; hexadecane; interleukin-1; neutrophil extracellular trap; arthritis; apoptosis
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Funding
- Austrian Science Fund (FWF) [J3102-B13]
- Lars Hiertas Minne foundation
- European Union [11,5142]
- EFPIA
- Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg [A41]
- DFG [GK SFB 643]
- K. und R. Wucherpfennigstiftung
- Austrian Science Fund (FWF) [J 3102] Funding Source: researchfish
- Austrian Science Fund (FWF) [J3102] Funding Source: Austrian Science Fund (FWF)
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Hydrocarbon oils such as pristane or hexadecane induce arthritis and lupus in rodents sharing clinical and pathological features with the human diseases rheumatoid arthritis and systemic lupus erythematosus, respectively. In pristane-induced lupus in the mouse induction of apoptosis and augmentation of type-I Interferon signalling by pristane have been suggested to contribute to pathology, whereas in pristane-induced arthritis (PIA) in the rat the pathological mechanisms are still elusive. Here we show that pristane induces cell death in rat and human cells. Increased numbers of apoptotic cells were found in draining lymph nodes of pristane-injected rats and increased percentages of apoptotic and necrotic cells were observed in peripheral blood. In addition, neutrophil extracellular trap formation was triggered by pristane and hexadecane in neutrophils. Because levels of interleukin (IL)-1 beta were elevated in sera of pristane-injected rats, with levels mirroring the course of PIA, we examined the effect of pristane at single cell level in vitro, using rat splenocytes and the human monocytic cell line THP-1. Pristane and other hydrocarbon oils induced IL-1 beta secretion in THP-1 cells as well as in rat splenocytes. The potassium channel inhibitor glibenclamide partly inhibited IL-1 beta induction, suggesting involvement of the inflammasome. Elevated levels of IL-1 alpha were also found in supernatants of cells treated with pristane and hexadecane. In conclusion, autoimmunogenic hydrocarbon oils induce various forms of cell death in rat and human cells. The higher serum IL-1 beta levels in pristane-injected animals might be caused by both inflammasome-dependent and -independent mechanisms, such as passive release from dying-cells and probably extracellular maturation of pro-IL-1 beta.
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