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The effect of anti-inflammatory properties of ferritin light chain on lipopolysaccharide-induced inflammatory response in murine macrophages

机译:铁蛋白轻链的抗炎特性对脂多糖诱导的小鼠巨噬细胞炎症反应的影响

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摘要

Ferritin light chain (FTL) reduces the free iron concentration by forming ferritin complexes with ferritin heavy chain (FTH). Thus, FTL competes with the Fenton reaction by acting as an antioxidant. In the present study, we determined that FTL influences the lipopolysaccharide (LPS)-induced inflammatory response. FTL protein expression was regulated by LPS stimulation in RAW264.7 cells. To investigate the role of FTL in LPS-activated murine macrophages, we established stable FTL-expressing cells and used shRNA to silence FTL expression in RAW264.7 cells. Overexpression of FTL significantly decreased the LPS-induced production of tumor necrosis factor alpha (TNF-a), interleukin 1(3 (IL-1(3), nitric oxide (NO) and prostaglandin E2 (PGE2). Additionally, overexpression of FTL decreased the LPS-induced increase of the intracellular labile iron pool (LIP) and reactive oxygen species (ROS). Moreover, FTL overexpression suppressed the LPS-induced activation of MAPKs and nuclear factor-KB (NF-kB). In contrast, knockdown of FTL by shRNA showed the reverse effects. Therefore, our results indicate that FTL plays an anti-inflammatory role in response to LPS in murine macrophages and may have therapeutic potential for treating inflammatory diseases.
机译:铁蛋白轻链(FTL)通过与铁蛋白重链(FTH)形成铁蛋白复合物来降低游离铁浓度。因此,FTL通过充当抗氧化剂与Fenton反应竞争。在本研究中,我们确定FTL影响脂多糖(LPS)诱导的炎症反应。 FTL蛋白表达受到RAW264.7细胞中LPS刺激的调节。为了研究FTL在LPS激活的小鼠巨噬细胞中的作用,我们建立了稳定的FTL表达细胞,并使用shRNA沉默了RAW264.7细胞中FTL的表达。 FTL的过表达显着降低了LPS诱导的肿瘤坏死因子α(TNF-a),白介素1(3(IL-1(3),一氧化氮(NO)和前列腺素E2(PGE2))的产生。降低了LPS诱导的细胞内不稳定铁池(LIP)和活性氧(ROS)的增加; FTL的过表达抑制了LPS诱导的MAPKs和核因子-KB(NF-kB)的激活。 shRNA对FTL的逆转录作用显示出相反的作用,因此,我们的研究结果表明FTL对小鼠巨噬细胞中的LPS有抗炎作用,可能具有治疗炎性疾病的潜力。

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