Radiation takes its Toll

Abstract

The ability to recognize and respond to universal molecular patterns on invading microorganisms allows our immune system to stay on high alert, sensing danger to our self-integrity. Our own damaged cells and tissues in pathological situations activate similar warning systems as microbes. In this way, the body is able to mount a response that is appropriate to the danger. Toll-like receptors are at the heart of this pattern recognition system that initiates innate pro-oxidant, pro-inflammatory signaling cascades and ultimately bridges recognition of danger to adaptive immunity. The acute inflammatory lesions that are formed segue into resolution of inflammation, repair and healing or, more dysfunctionally, into chronic inflammation, autoimmunity, excessive tissue damage and carcinogenesis. Redox is at the nexus of this decision making process and is the point at which ionizing radiation initially intercepts to trigger similar responses to self-damage. In this review we discuss our current understanding of how radiation-damaged cells interact with Toll-like receptors and how the immune systems interprets these radiation-induced danger signals in the context of whole-body exposures and during local tumor irradiation.

Lipoxins: nature's way to resolve inflammation

“… 44 , 94 , 95 A combination of several chemotherapeutic agents is currently used in treatment of PDAC, but unfortunately they have significant side effects, even though increasing life expectancy by 6 months. 96 , 97 Hence, there is a need to find other targets to treat PDAC. Transcriptional factors like nuclear factor of activated T-cells, Nrf2, and NFκB have been recently identified as potential targets to cure PDAC.…”

Involvement of reactive oxygen species in ionizing radiation–induced upregulation of cell surface Toll-like receptor 2 and 4 expression in human monocytic cells

“…TLRs play major roles in antibacterial and antiviral immunity. Furthermore, recent studies have shown the involvement of TLRs in radiation response, including radiation-induced tissue damage and the efficacy of cancer radiotherapy [ 6 , 9 , 11 , 12 ]. We have previously reported that ionizing radiation affects the expressions and responses of TLR2 and TLR4 in human monocytic THP1 cells [ 13 ].…”

“…Furthermore, it has been reported that TLR2–/– mice are more susceptible to ionizing radiation–induced mortality because of severe bone marrow cell loss, and wild-type mice pre-treated with TLR2 agonist show resistance to ionizing-induced motility [ 6 ]. In addition to the exogenous danger molecules PAMPs, TLRs recognize endogenous danger molecules, the so-called damage-associated molecular patterns (DAMPs) [ 8 , 9 ]. It has been shown that the responses of TLRs to DAMPs such as host RNA and high-mobility group box 1 (HMGB1), which are released from damaged cells, also cause biological responses, including the radiation response [ 8 – 12 ].…”

The Role of Lymphocytes in Radiotherapy-Induced Adverse Late Effects in the Lung

“…For radiation-induced lung injury it has been described that the released DAMPs act through signaling via P2X, P2Y receptors, toll-like receptors (TLR-2 and TLR-4), receptor for advanced glycation end-products, and NOD-like receptors (NLRP3), respectively (152). Consistent with a role of TLR signaling in radiation-induced lung disease, Myd88 knockout mice displayed increased as well decreased fibrosis development depending on the type of injury induced.…”