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NLRP3 炎性小体-白介素 1β 轴在葡萄膜黑色素瘤中的作用。

The NLRP3 inflammasome - interleukin 1β axis in uveal melanoma.

机构信息

Retina Service, Ines and Fred Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.

出版信息

FEBS Open Bio. 2023 Mar;13(3):545-555. doi: 10.1002/2211-5463.13566. Epub 2023 Feb 12.

Abstract

Uveal melanoma (UM) is the most common primary intraocular cancer in the adult population. Recent studies suggested that the NLRP3 inflammasome could be a therapeutic target for cutaneous melanoma (CM), but the role of NLRP3 in UM remains unknown. Here, we analyzed the NLRP3-IL-1β axis in 5 UM and 4 CM cell lines. Expression of NLRP3 mRNA in UM and CM was low, and expression in UM was lower than in CM (P < 0.001). NLRP3 protein levels were below detection limit for all cell lines. UM exhibited lower baseline IL-1β secretion than CM, especially when compared to the Hs294t cell line (P < 0.05). Bioinformatic analysis of human tumor samples showed that UM has significantly lower expression of NLRP3 and IL-1β compared with CM. In conclusion, our work shows evidence of extremely low NLRP3 expression and IL-1β secretion by melanoma cells and highlight differences between CM and UM.

摘要

葡萄膜黑色素瘤 (UM) 是成年人中最常见的原发性眼内肿瘤。最近的研究表明,NLRP3 炎性体可能是皮肤黑色素瘤 (CM) 的治疗靶点,但 NLRP3 在 UM 中的作用尚不清楚。在这里,我们分析了 5 种 UM 和 4 种 CM 细胞系中的 NLRP3-IL-1β 轴。UM 和 CM 中 NLRP3 mRNA 的表达水平较低,且 UM 中的表达水平低于 CM(P<0.001)。所有细胞系的 NLRP3 蛋白水平均低于检测下限。UM 显示出比 CM 更低的基础 IL-1β 分泌水平,与 Hs294t 细胞系相比尤为明显(P<0.05)。对人类肿瘤样本的生物信息学分析表明,与 CM 相比,UM 中 NLRP3 和 IL-1β 的表达水平显著降低。综上所述,我们的工作表明黑色素瘤细胞 NLRP3 的表达和 IL-1β 的分泌极低,并突出了 CM 和 UM 之间的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b210/9989921/43ec1d9e8327/FEB4-13-545-g003.jpg

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