What is it about?
We built a mathematical model of arachidonic acid metabolic pathway in inflammatory cells, producing eicosanoids - prostaglandins and leukotrienes. Based on the differences in enzyme expressions of two enzymes in this pathway we defined model 5 populations simulating non-asthmatics as well as one aspirin tolerant and 3 intolerant asthmatic populations. Simulations were carried out for two states of the model - state of no-inflammation and inflammation. Model results were compared with the measured ones and new predictions were proposed. Especially, the dynamic eicosanoid production was predicted in response to NSAIDs for different model populations and the model states of no-inflammation and inflammation. In this way, the sensitiviy to NSAIDs of each model population was investigated.
Featured Image
Why is it important?
In spite of accumulating experimental and clinical results the molecular and cellular mechanisms, which induce and initiate processes in aspirin induced asthma, are still not completely elucidated and understood. In the past, experimental and clinical research was primarily focused on a single level, either on concerning the gene, molecular, cellular or tissue/organ level. Theoretical analyses and predictions attained from mathematical models, such as ours, integrate the accumulated knowledge of these different levels of research. Therefore, the mathematical model analysis might serve as suitable tool aiding to figure out and test new hypotheses, check molecular mechanisms, analyse experimental results, guide novel experiments as well as give ideas for new methods and tools for diagnosing and treatment diseases on a multiscale level.
Perspectives
Our mathematical model represents a step forward towards multiscale models of the lung. In such multi-cellular models airway smooth muscle cells will be coupled with cells involved in inflammation via inflammatory mediators acting on airway smooth muscle cells by contraction/relaxation mechanisms. These multiscale models might elucidate the underlying functional and molecular abnormalities, which result from complex cellular alterations in aspirin intolerant asthma. Those complex alterations are expressed in terms of inter- and intracellular signalling of metabolism due to over- and under-expression of genes, gene products, consider possible input stimuli which finally integrate and reveal a unique message in response to external and internal events, e.g. an inflammatory disease. Ambitious efforts will be to extent our recent model to facilitate meaningful estimations for an individual risk of bronchoconstriction regarding asthmatic patients, supposed to be intolerant to aspirin, ideally with regard to the type and dose of the NSAID as well as his/her acute original condition of inflammation and bronchial hyper-responsiveness.
Dr Ales Fajmut
Univerza v Mariboru
Read the Original
This page is a summary of: Dynamic model of eicosanoid production with special reference to non-steroidal anti-inflammatory drug-triggered hypersensitivity, IET Systems Biology, October 2015, the Institution of Engineering and Technology (the IET),
DOI: 10.1049/iet-syb.2014.0037.
You can read the full text:
Contributors
The following have contributed to this page
