Progresses in radiation protective agents targeting Toll-like receptor pathway / 中华放射医学与防护杂志

ABSTRACT

Acute radiation exposure usually causes severe dysfunction in various tissues of the organism, among which hematopoiesis, digestion, skin, cardiovascular and nervous system are most obviously affected, often leading to extensive apoptosis and acute radiation syndrome. Apoptosis inhibition or loss could increase proliferation of tumor cells through p53 and NF-κB pathways. Toll-like receptors ( TLRs) are a class of protein molecules involved in non-specific immunity. Up-regulation of the NF-κB pathway results in a significant increase in the radioresistance of cells. TLR4 has a basal cell radiation damage protection effect. Traditional TLR4 agonist lipopolysaccharide is limited in clinical application due to severe toxicity. Recently, some new TLRs agonists have been reported, which have protective effects against the lethal effects of ionizing radiation and lower toxic side effects. Among them, TLR2, TLR4, TLR5 and TLR9 play key roles in radiation protection, such as TLR2 receptor agonist bacterial lipoprotein (BLP), TLR4 receptor agonist heat-activated Salmonella typhimurium (HKST), TLR5 receptor agonism Bacterial flagellin and TLR9 receptor agonist. However, those different TLRs recognize specific components of the pathogen and thus initiate different downstream signaling pathways with different protective effects.