Cell death and cytokine production induced by autoimmunogenic hydrocarbon oils

Abstract

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)-1β 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-1β secretion in THP-1 cells as well as in rat splenocytes. The potassium channel inhibitor glibenclamide partly inhibited IL-1β induction, suggesting involvement of the inflammasome. Elevated levels of IL-1α 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-1β 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-1β.

Keywords::

• Pristane
• hexadecane
• interleukin-1
• neutrophil extracellular trap
• arthritis
• apoptosis

Acknowledgements

This research was funded by the Austrian Science Fund (FWF) (Project J3102-B13), the Lars Hiertas Minne foundation, and by the Innovative Medicines Initiative Joint Undertaking under grant agreement No. 11,5142, resources of which are composed of financial contribution from the European Union's 7^th Framework Programme and EFPIA companies in kind contribution. This project was also supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg, project A41 and by the training Grant GK SFB 643 from the DFG and the K. und R. Wucherpfennigstiftung.

Declaration of interest : The authors declare no conflict of interests. The authors are responsible for the content and the writing of this paper.