Download Modulation of inflammation by ionising radiation – impact on non

Modulation of inflammation by ionising radiation – impact on non-cancer and
cancer diseases
Benjamin Frey1, Roland Wunderlich1, Lisa Deloch1, Paul F. Rühle1, Nina
Werthmöller1, Anja Derer1, Yvonne Rubner1, Franz Rödel2, Claudia Fournier3, Rainer
Fietkau1, Udo S. Gaipl1
1 Department of Radiation Oncology, University Hospital Erlangen, FriedrichAlexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
2 Department of Radiotherapy and Oncology, Goethe-University of Frankfurt,
Frankfurt am Main, Germany.
3 Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research,
Darmstadt, Germany.
[email protected]
Inflammatory reactions consistently emerge in the body. They result from temporal
changes in the tissue microenvironment in response to damage. The latter can be
caused by radiation of different doses, dose rates and quality. Recent work suggests
that low and intermediate dose of radiation exerts anti-inflammatory effects in a preexisting inflammatory environment and that higher doses of radiation foster further
inflammation and especially specific immune activation against components of the
damaged tissue. Released danger signals such as heat shock protein70 (Hsp70), highmobility group box 1 protein (HMGB1), and adenosine triphosphate (ATP) seem to
be key players in driving the consecutive immune modulation after exposing tissues
to noxious agents.
The talk will focus on how low and intermediate doses of irradiation impact on
macrophage viability, their inflammatory phenotype and function. Macrophages are
cells of the innate immune system and key players in initiation and resolution of
inflammation. Further, data will be presented that the inflammatory and erosive area
in human-TNF-alpha transgenic mice, that develop a chronic polyarthritis, can be
reduced by an intermediate dose of X-ray. In the second part, the role of danger
signals in the induction of non-targeted effects of ionising radiation alone and
especially with further immune stimulation will be outlined. Data will be presented
that specific and systemic anti-tumour immune responses are inducible by
modification of the phenotype of tumour cells and their microenvironment by
radiation.
The knowledge on how radiation shifts an inflammatory environment in an antiinflammatory one and on how specific immune reactions are started after exposure to
higher doses of radiation are of value for radiation protection issues, improvements of
therapies against cancer and for a deeper understanding of radiation-induced
carcinogenesis and non-cancer effects. Since radiation modulates inflammation and
the latter impacts on non-cancer and cancer diseases, future research should focus
intensively on mechanisms of interactions between radiation-induced DNA-damage
and inflammatory events.