IL-6 in inflammation, autoimmunity and cancer.
IL-6 in inflammation, autoimmunity and cancer.
复制标题
白细胞介素 - 6在炎症、自身免疫和癌症中的作用（此处如果单纯翻译原句是“白细胞介素 - 6在炎症、自身免疫和癌症中”，但感觉原句可能是关于白细胞介素 - 6在这些方面的相关研究或作用等主题的一部分，所以补充“的作用”使译文更通顺合理）
DOI：
10.1093/intimm/dxaa078
复制
发表时间：
2021-03-01
影响因子：
4.4
通讯作者：
Hirano T
中科院分区：
文献类型：
--
作者：
Hirano T
白细胞介素-6（IL-6）：免疫应答和疾病的关系IL-6参与免疫应答和炎症、造血、骨代谢和胚胎发育。IL-6在慢性炎症（与慢性炎症性疾病、自身免疫性疾病和癌症密切相关）中发挥作用，甚至在2019冠状病毒病（COVID-19）的细胞因子风暴中发挥作用。免疫应答和伤口愈合期间的急性炎症是良好控制的应答，而慢性炎症和细胞因子风暴是不受控制的炎症应答。非免疫细胞和免疫细胞、细胞因子如IL-1β、IL-6和肿瘤坏死因子α（TNFα）以及转录因子核因子-κ B（NF-κB）和信号转导子和转录激活子3（STAT 3）在炎症中发挥核心作用。NF-κB和STAT 3之间的协同相互作用诱导NF-κB的过度活化，随后产生各种炎性细胞因子。由于IL-6是NF-κB靶点，因此在非免疫细胞中NF-κB和STAT 3的同时激活通过IL-6-STAT 3轴触发NF-κB激活的正反馈环。这种正反馈回路被称为IL-6放大器（IL-6 amplifier，IL-6放大器），是局部启动模型中的关键参与者，该模型指出，局部启动者，如衰老，肥胖，应激源，感染，损伤和吸烟，通过促进非免疫细胞和免疫细胞之间的相互作用引发疾病。该模型反对认为自身免疫和肿瘤发生分别由组织特异性免疫耐受和致癌突变的破坏触发的教条。IL-6 β被多种局部引发剂激活，表明IL-6-STAT 3轴是治疗疾病的关键靶标。
IL-6: a nexus for immune responses and disease IL-6 is involved both in immune responses and in inflammation, hematopoiesis, bone metabolism and embryonic development. IL-6 plays roles in chronic inflammation (closely related to chronic inflammatory diseases, autoimmune diseases and cancer) and even in the cytokine storm of corona virus disease 2019 (COVID-19). Acute inflammation during the immune response and wound healing is a well-controlled response, whereas chronic inflammation and the cytokine storm are uncontrolled inflammatory responses. Non-immune and immune cells, cytokines such as IL-1β, IL-6 and tumor necrosis factor alpha (TNFα) and transcription factors nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play central roles in inflammation. Synergistic interactions between NF-κB and STAT3 induce the hyper-activation of NF-κB followed by the production of various inflammatory cytokines. Because IL-6 is an NF-κB target, simultaneous activation of NF-κB and STAT3 in non-immune cells triggers a positive feedback loop of NF-κB activation by the IL-6–STAT3 axis. This positive feedback loop is called the IL-6 amplifier (IL-6 Amp) and is a key player in the local initiation model, which states that local initiators, such as senescence, obesity, stressors, infection, injury and smoking, trigger diseases by promoting interactions between non-immune cells and immune cells. This model counters dogma that holds that autoimmunity and oncogenesis are triggered by the breakdown of tissue-specific immune tolerance and oncogenic mutations, respectively. The IL-6 Amp is activated by a variety of local initiators, demonstrating that the IL-6–STAT3 axis is a critical target for treating diseases.
登录
查看更多内容
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
11.4
作者：
AKIRA, S;ISSHIKI, H;KISHIMOTO, T
通讯作者：
KISHIMOTO, T
影响因子：
20.3
作者：
BATAILLE, R;BARLOGIE, B;KLEIN, B
通讯作者：
KLEIN, B
影响因子：
3.7
作者：
Anand, Preetha;Kunnumakara, Ajaikumar B.;Sundaram, Chitra;Harikumar, Kuzhuvelil B.;Tharakan, Sheeja T.;Lai, Oiki S.;Sung, Bokyung;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.