Experimental and theoretical analysis of cytokine release for the study of radiation-induced bystander effect

Abstract

This study solved some of the methodological doubts concerning the study of bystander effects by means of the medium transfer technique; moreover it also highlighted some experimental aspects that need to be considered when approaching this sort of experiments.

Reactive oxygen species-induced release of signalling factors in irradiated cells triggers membrane signalling and calcium influx in bystander cells

“…Due to the short half lives of these radical species, it is likely that long lived soluble factors are induced by these ROS and released into the medium. Cytokines such as interleukins and TGFβ have been shown to be involved in bystander responses (Iyer et al 2000;Osterreicher et al 2003;Facoetti et al 2006;Shao et al 2008;Facoetti et al 2009) and have been shown to be induced by ROS (Iyer et al 2000).…”

“…Bystander effects have been shown to be mediated by a variety of signalling factors including reactive oxygen species (ROS) Wu et al 1999; Azzam et al 2002;Lyng et al 2006;Harada et al 2008), nitric oxide (NO) (Matsumoto et al 2001;Shao et al 2002;Harada et al 2008), second messengers like calcium (Lyng et al 2000(Lyng et al , 2002Lyng et al 2006;Shao et al 2006), cytokines such as transforming growth factor beta (TGFβ) (Iyer et al 2000;Shao et al 2008) and interleukins (Osterreicher et al 2003;Facoetti et al 2006;Facoetti et al 2009) and tumour necrosis factor alpha (TNF-α) and tumor necrosis (TNF)-related apoptosis-inducing ligand (TRAIL) death inducing pathways (Shareef et al 2007;Luce et al 2009). In addition, cyclooxygenase-2 (COX-2) (Zhou et al 2005;Hei et al 2008), Nuclear Factor KappaB (NFkB) (Azzam et al 2002;Zhou et al 2008) and mitogen-activated protein (MAP) kinase (Azzam et al 2002;Zhou et al 2005;Lyng et al 2006) signalling have all been shown to be involved in bystander responses.…”

The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

“…Different profile of the production of interleukin 6 by HCT116 p53+/+ and p53−/− cells Interleukins 6 and 8 have been suggested as potential mediators of bystander effects [44]. Using ELISA tests we assayed the concentration in culture medium of both cytokines released by irradiated and/or bystander cells 24 and 48 h after exposure to different doses of X-rays.…”

Exosomes Are Involved in Mediating Radiation Induced Bystander Signaling in Human Keratinocyte Cells

“…Bystander signals may be transferred to surrounding cells either by gap junctional intercellular communication or by the production of soluble extracellular factors released from irradiated cells. Soluble signaling factors such as reactive oxygen species (ROS) (8)(9)(10)(11)(12), nitric oxide (NO) (12)(13)(14), secondary messengers like calcium (4,(8)(9)(10), cytokines such as interleukins (15)(16)(17), TGFb (18,19), TNFa and TRAIL (20,21) have been found to play a major role in radiation-induced bystander effects. A new mechanism for communication by soluble factors could be by intercellular communication by exosomes.…”