Effect of immunostimulatory RNA on the fibrosis development in Bleomycin- or LPS-induced mouse models.

Aleksandra V Sen'kova, Ali Bishani, Innokenty A Savin, Marina A Zenkova, Elena L Chernolovskaya
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Abstract

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

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免疫刺激 RNA 对博莱霉素或 LPS 诱导的小鼠模型纤维化发展的影响
此前,我们曾描述过一种具有 3'- 三核苷酸悬垂的 19 碱基对双链 RNA(免疫刺激 RNA,isRNA)。这种分子对癌细胞有显著的抗增殖作用,能抑制肿瘤生长,并通过诱导细胞因子和干扰素的产生引起免疫刺激和抗病毒反应。在本研究中,我们使用不同的诱导方案,比较了 BLM 或 LPS 在小鼠体内引发肺纤维化的效率。然后,我们比较了预防或治疗方案中使用的 isRNA 对选定的 BLM 和 LPS 诱导的小鼠模型中纤维化发展的影响,结果表明,isRNA 可用于伴有炎症发展和纤维化形成风险的病理条件,且无不良副作用。应用 isRNA 的预防性疗法有利于预防肺纤维化的发展。
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