May the inflammatory response be considered as an example of non DNA-damage driven system?

The inflammatory pathway has been widely studied over the past 25 years highlighting its complex and highly interlaced relationships with all main cell functions, ranging from cell survival- to death- related ones, and its well-established involvement in the formation of several tumours. One of the key aspects of this pathway, and its key player NF-kB, is the response to a wide range of stimuli, both in terms of quality (signalling proteins, environmental stress, ionizing radiation) and in terms of intensity, switching cell states and equilibrium, e.g. from proliferation to apoptosis. Several works in literature addressed the effects of different ionizing radiation qualities (e.g. [1]), the role of LPS in chronic and acute inflammation, and the role of other molecules able to trigger a cascade of signals, which in turn leads to the release of a myriad of both intra- and extra- cellular signals. In this work we adopted an integrated experimental/theoretical approach to investigate this complex scenario, with the aim of better understanding the non-linear temporal dynamics of the different key players involved. Molecules related to NF-kB and its pathway have been measured after X-ray exposure (up to 5 Gy) or LPS treatment (0, 5 and 50 ng/ml), through the use of commercially available ELISA assay kit, western blot or immunofluorescence, to unravel their spatial localization and the temporal dynamics of their activation. Preliminary results indicate that the X-ray radiation insult might not be the major stress affecting the cells (up to 5 Gy), and could be hidden by other co-existing stimuli (such as medium change, LPS treatment, environmental stress, etc), confirming the complexity of the inflammatory pathway and suggesting that its activation might be driven not only by the DNA damage response induced by ionizing radiation but also by mitochondrial and endoplasmic reticulum dysfunction.