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Lysosomal Ca2+ signaling regulates high glucose-mediated interleukin-1β secretion via transcription factor EB in human monocytic cells
Tseng H.H.L.2; Vong C.T.2; Kwan Y.W.1; Lee S.M.-Y.2; Hoi M.P.M.2
2017-09-15
Source PublicationFrontiers in Immunology
ISSN16643224
Volume8Issue:SEP
AbstractAberrant 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 Ca homeostasis and lysosomal exocytosis. We found that high glucose (HG; 30 mM glucose for 48 h) altered Ca2+ homeostasis by reducing lysosomal Ca concentration that appeared to be resulted from Ca moving out of lysosomes into cytosol in human monocytic cell lines, U937 and THP-1 cells. Moreover, HG-induced lysosomal Ca-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 Ca signals through calcineurin/TFEB pathway, thus contributing to IL-1β secretion in human monocytic cells.
KeywordCa2+ homeostasis High glucose Interleukin-1β Lysosomal Ca2+ Lysosomal exocytosis Monocytes
DOI10.3389/fimmu.2017.01161
URLView the original
Language英語
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Chinese University of Hong Kong
2.University of Macau
First Author AffilicationUniversity of Macau
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GB/T 7714
Tseng H.H.L.,Vong C.T.,Kwan Y.W.,et al. Lysosomal Ca2+ signaling regulates high glucose-mediated interleukin-1β secretion via transcription factor EB in human monocytic cells[J]. Frontiers in Immunology,2017,8(SEP).
APA Tseng H.H.L.,Vong C.T.,Kwan Y.W.,Lee S.M.-Y.,&Hoi M.P.M..(2017).Lysosomal Ca2+ signaling regulates high glucose-mediated interleukin-1β secretion via transcription factor EB in human monocytic cells.Frontiers in Immunology,8(SEP).
MLA Tseng H.H.L.,et al."Lysosomal Ca2+ signaling regulates high glucose-mediated interleukin-1β secretion via transcription factor EB in human monocytic cells".Frontiers in Immunology 8.SEP(2017).
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