UM
Lysosomal Ca2+ Signaling REgulates High Glucose-Mediated Interleukin-1 beta Secretion via Transcription Factor EB in Human Monocytic Cells
Tseng, Hisa Hui Ling; Vong, Chi Teng; Kwan, Yiu Wa; Lee, Simon Ming-Yuen; Hoi, Maggie Pui Man
2017-09-15
Source PublicationFRONTIERS IN IMMUNOLOGY
ISSN1664-3224
Volume8
AbstractAberrant activation of the innate immune system, including NOD-like receptor pyrindomain containing 3 (NLRP3) inflammasome-dependent interleukin-1 beta (IL-1 beta) secretion, has been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and itscomplication. Our previous study demonstrated that hyperglycemia, a hallmark characteristic of T2DM, induced NLRP3 inflammasome-dependent caspase-1 activation and IL-1 beta maturation in human monocytic cells. In this study, we examined the underlying mechanisms of secreting IL-1 beta 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-1 beta 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-1 beta secretion in human monocytic cells.
Keywordhigh glucose lysosomal Ca2+ Ca2+ homeostasis lysosomal exocytosis interleukin-1 beta monocytes
DOI10.3389/fimmu.2017.01161
URLView the original
Indexed BySCI
Language英语
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000410747500001
PublisherFRONTIERS MEDIA SA
The Source to ArticleWOS
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Tseng, Hisa Hui Ling,Vong, Chi Teng,Kwan, Yiu Wa,et al. Lysosomal Ca2+ Signaling REgulates High Glucose-Mediated Interleukin-1 beta Secretion via Transcription Factor EB in Human Monocytic Cells[J]. FRONTIERS IN IMMUNOLOGY,2017,8.
APA Tseng, Hisa Hui Ling,Vong, Chi Teng,Kwan, Yiu Wa,Lee, Simon Ming-Yuen,&Hoi, Maggie Pui Man.(2017).Lysosomal Ca2+ Signaling REgulates High Glucose-Mediated Interleukin-1 beta Secretion via Transcription Factor EB in Human Monocytic Cells.FRONTIERS IN IMMUNOLOGY,8.
MLA Tseng, Hisa Hui Ling,et al."Lysosomal Ca2+ Signaling REgulates High Glucose-Mediated Interleukin-1 beta Secretion via Transcription Factor EB in Human Monocytic Cells".FRONTIERS IN IMMUNOLOGY 8(2017).
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