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Nucleic acid-binding polymers as anti-inflammatory agents

机译:核酸结合聚合物作为抗炎药

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摘要

Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids.
机译:死亡和垂死的细胞释放核酸。这些细胞外RNA和DNA可以被炎性细胞吸收并激活多种核酸感应的toll样受体(TLR3、7、8和9)。这些TLR的不适当激活会引发多种炎症和自身免疫性疾病。 TLR家族的冗余性鼓励我们寻找可以中和任何核酸的促炎作用的材料,而无论其序列,结构或化学性质如何。本文中,我们证明了某些核酸结合聚合物可以抑制所有核酸感应TLR的激活,无论它们是否识别ssRNA,dsRNA或低甲基化的DNA。此外,在小鼠的急性中毒性休克模型中,全身施用这种聚合物可以预防由促炎性核酸引起的致命性肝损伤。因此,这些聚合物代表了一类新型的抗炎剂,其可以充当分子清除剂以中和各种核酸的促炎作用。

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