Calcium Signalling and inflammation
In mammals, the innate immune system-mediated inflammation is a part of the first non-specific defense barriers of host against invading pathogens and tissue damage. Hallmarks of the innate immunity encompass the ability to recognize and kill pathogenic microorganisms early during infection. These processes are based primarily on the presence of infiltrating immune and inflammatory cells, such as antigen-presenting dendritic cells, T-lymphocytes, professional phagocytes (macrophages, granulocytes), in the inflammatory microenvironment. Over-activation of host cells, and notably phagocytes, is extremely deleterious due to internal dysfunction related to modification of protein expression/function and can lead to an inappropriate secretion of their cytotoxic products (reactive oxygen species, matrix-degrading enzymes) and pro-inflammatory mediators (cytokines, chemokines). Unresolved inflammation causes erosion of tissue integrity and contributes to the development of common chronic inflammation diseases such as rheumatoid arthritis, asthma, bronchial hyper-reactivity, and atherosclerosis. Furthermore, persistent inflammation promotes carcinogenesis and increases the risk of cancer. Because all these disorders have a substantial societal impact and are recognized as leading causes of mortality, they are a paramount of basic science research and clinical investigations.
The aims of the “Calcium Signaling and Inflammation Group” are to determine molecular mechanisms that underpin the process of inflammation and dissect transduction pathways in cells linked to inflammatory diseases. In collaboration with national and international institutions, our research relies on an interdisciplinary approach (computational modeling, biochemistry, genomics, proteomics (patho) physiology) to ensure the most exact depiction and to facilitate the understanding of the complex mechanistic basis of chronic inflammation.
We currently focus on the three following topics:
- Regulation of the NADPH oxidase through calcium-S100A8/A9 signalling pathway in human neutrophils.
- Regulation of neutrophil pro-inflammatory functions: role of exocytotic proteins.
- Involvement of micronutrients and cytokines in the early steps of atherosclerosis development.
The long term impact of such research is to provide the foundation for the elucidation of new therapeutic targets for chronic inflammatory diseases in humans and foster the development of new paradigms in pathophysiology.
