Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.
Zebrafish tissue injury causes upregulation of interleukin-1 and caspase-dependent amplification of the inflammatory response.
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DOI：
10.1242/dmm.013029
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发表时间：
2014-02
影响因子：
4.3
通讯作者：
Wilson HL
中科院分区：
文献类型：
--
作者：
Ogryzko NV;Hoggett EE;Solaymani-Kohal S;Tazzyman S;Chico TJ;Renshaw SA;Wilson HL
白细胞介素-1（IL-1），炎症的“看门人”，是信号级联中的顶端细胞因子，驱动对损伤或感染的早期反应。IL-1的表达、加工和分泌受到严格控制，并且失调的IL-1信号传导已经涉及从动脉粥样硬化到感染并发症的许多病理学。我们对这些过程的理解来自于体外单核细胞培养模型，如细胞系或原代分离株，其中已经描述了IL-1分泌机制的范围和谱。因此，我们研究了斑马鱼胚胎是否为研究IL-1介导的炎症提供了合适的体内模型。在结构上，斑马鱼IL-1β与其人类对应物共享富含β-片层的三叶形结构。从功能上讲，IL-1β的白细胞表达仅在损伤后才能检测到，损伤激活了整个斑马鱼胚胎的白细胞。巨噬细胞和中性粒细胞的迁移被caspase-1或P2 X7抑制剂减弱，这类似地抑制了损伤部位NF-κB的活化。斑马鱼为研究炎症性疾病中的IL-1β通路提供了一种新的多功能模型，并应提供体内IL-1生物学的独特见解。
Interleukin-1 (IL-1), the ‘gatekeeper’ of inflammation, is the apical cytokine in a signalling cascade that drives the early response to injury or infection. Expression, processing and secretion of IL-1 are tightly controlled, and dysregulated IL-1 signalling has been implicated in a number of pathologies ranging from atherosclerosis to complications of infection. Our understanding of these processes comes from in vitro monocytic cell culture models as lines or primary isolates, in which a range and spectra of IL-1 secretion mechanisms have been described. We therefore investigated whether zebrafish embryos provide a suitable in vivo model for studying IL-1-mediated inflammation. Structurally, zebrafish IL-1β shares a β-sheet-rich trefoil structure with its human counterpart. Functionally, leukocyte expression of IL-1β was detectable only following injury, which activated leukocytes throughout zebrafish embryos. Migration of macrophages and neutrophils was attenuated by inhibitors of either caspase-1 or P2X7, which similarly inhibited the activation of NF-κB at the site of injury. Zebrafish offer a new and versatile model to study the IL-1β pathway in inflammatory disease and should offer unique insights into IL-1 biology in vivo.
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DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
11.1
作者：
Dinarello CA
通讯作者：
Dinarello CA
影响因子：
14.8
作者：
Kelley, Lawrence A.;Sternberg, Michael J. E.
通讯作者：
Sternberg, Michael J. E.
影响因子：
9.8
作者：
Feng, Yi;Santoriello, Cristina;Martin, Paul
通讯作者：
Martin, Paul
影响因子：
3.6
作者：
Lopez-Castejon, Gloria;Young, Mark T.;Mulero, Victoriano
通讯作者：
Mulero, Victoriano