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Lysosomal Ca2+ Signaling Regulates High Glucose-Mediated Interleukin-1β Secretion via Transcription Factor EB in Human Monocytic Cells
Hisa Hui Ling Tseng1; Chi Teng Vong1; Yiu Wa Kwan2; Simon Ming Yuen Lee1; Maggie Pui Man Hoi1
2017-11
Source PublicationPLANT JOURNAL
ISSN0960-7412
Volume92Issue:3Pages:452-468
Abstract

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.

KeywordHigh Glucose Lysosomal Ca2++++ Ca2++++ Homeostasis Lysosomal Exocytosis Interleukin-1β Monocytes
DOI10.3389/fimmu.2017.01161
Indexed BySCI
Language英语
WOS Research AreaPlant Sciences
WOS SubjectPlant Sciences
WOS IDWOS:000412932100010
Fulltext Access
Citation statistics
Cited Times [WOS]:48   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau
2.Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Hisa Hui Ling Tseng,Chi Teng Vong,Yiu Wa Kwan,et al. Lysosomal Ca2+ Signaling Regulates High Glucose-Mediated Interleukin-1β Secretion via Transcription Factor EB in Human Monocytic Cells[J]. PLANT JOURNAL,2017,92(3):452-468.
APA Hisa Hui Ling Tseng,Chi Teng Vong,Yiu Wa Kwan,Simon Ming Yuen Lee,&Maggie Pui Man Hoi.(2017).Lysosomal Ca2+ Signaling Regulates High Glucose-Mediated Interleukin-1β Secretion via Transcription Factor EB in Human Monocytic Cells.PLANT JOURNAL,92(3),452-468.
MLA Hisa Hui Ling Tseng,et al."Lysosomal Ca2+ Signaling Regulates High Glucose-Mediated Interleukin-1β Secretion via Transcription Factor EB in Human Monocytic Cells".PLANT JOURNAL 92.3(2017):452-468.
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