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Theoretical Studies on the Engagement of Interleukin 18 in the Immuno-Inflammatory Processes Underlying Atherosclerosis

Department of Clinical Biochemistry and Laboratory Medicine, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznan, Poland
Institute of Computing Science, Poznan University of Technology, Piotrowo 2, 60-965 Poznan, Poland
Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(11), 3476;
Received: 30 September 2018 / Revised: 30 October 2018 / Accepted: 31 October 2018 / Published: 5 November 2018
(This article belongs to the Special Issue The Interleukins in Health and Disease)
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Interleukin 18 (IL-18) is one of the pro-inflammatory cytokines expressed by macrophages, suggesting that it plays important physiological and immunological functions, among the others: stimulation of natural killers (NKs) and T cells to interferon gamma (IFN- γ ) synthesis. IL-18 was originally identified as interferon gamma inducing factor and now it is recognized as multifunctional cytokine, which has a role in regulation of innate and adaptive immune responses. Therefore, in order to investigate IL-18 contribution to the immuno-inflammatory processes underlying atherosclerosis, a systems approach has been used in our studies. For this purpose, a model of the studied phenomenon, including selected pathways, based on the Petri-net theory, has been created and then analyzed. Two pathways of IL-18 synthesis have been distinguished: caspase 1-dependent pathway and caspase 1-independent pathway. The analysis based on t-invariants allowed for determining interesting dependencies between IL-18 and different types of macrophages: M1 are involved in positive regulation of IL-18, while M2 are involved in negative regulation of IL-18. Moreover, the obtained results showed that IL-18 is produced more often via caspase 1-independent pathway than caspase 1-dependent pathway. Furthermore, we found that this last pathway may be associated with caspase 8 action. View Full-Text
Keywords: interleukin 18; macrophages; atherosclerosis; modeling; Petri nets; t-invariants interleukin 18; macrophages; atherosclerosis; modeling; Petri nets; t-invariants

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Formanowicz, D.; Gutowska, K.; Formanowicz, P. Theoretical Studies on the Engagement of Interleukin 18 in the Immuno-Inflammatory Processes Underlying Atherosclerosis. Int. J. Mol. Sci. 2018, 19, 3476.

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