Lysosomal Ca2+ Signaling Regulates High Glucose-Mediated Interleukin-1β Secretion via Transcription Factor EB in Human Monocytic Cells
Publication in refereed journal

香港中文大學研究人員
替代計量分析
.

其它資訊
摘要Aberrant activation of the innate immune system, including NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome-dependent interleukin-1β (IL-1β) secretion, has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and its complication. Our previous study demonstrated that hyperglycemia, a hallmark characteristic of T2DM, induced NLRP3 inflammasome-dependent caspase-1 activation and IL-1β maturation in human monocytic cells. In this study, we examined the underlying mechanisms of secreting IL-1β during hyperglycemia, with a focus on the alteration of Ca2+ homeostasis and lysosomal exocytosis. We found that high glucose (HG; 30 mM glucose for 48 h) altered Ca2+ homeostasis by reducing lysosomal Ca2+ concentration that appeared to be resulted from Ca2+ moving out of lysosomes into cytosol in human monocytic cell lines, U937 and THP-1 cells. Moreover, HG-induced lysosomal Ca2+-dependent mature IL-1β release was strongly correlated with the activation and upregulation of two lysosomal marker proteins, cathepsin D and lysosomal-associated membrane protein-1 (LAMP-1). This involved calcineurin/transcription factor EB (TFEB) pathway and its target genes, cathepsin B, cathepsin D, and LAMP-1, to mediate lysosomal exocytosis. Therefore in this study, we revealed a novel mechanism of HG-induced lysosomal exocytosis which was regulated by lysosomal Ca2+ signals through calcineurin/TFEB pathway, thus contributing to IL-1β secretion in human monocytic cells.
著者Hisa Hui Ling TSENG, Chi Teng VONG, Yiu Wa KWAN, Simon Ming-Yuen LEE, Maggie Pui Man HOI
期刊名稱Frontiers in Immunology
出版年份2017
月份9
日期15
卷號8
文章號碼1161
國際標準期刊號1664-3224
語言英式英語

上次更新時間 2020-16-09 於 00:51