PMID- 28970837
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - Lysosomal Ca(2+) Signaling Regulates High Glucose-Mediated Interleukin-1beta 
      Secretion via Transcription Factor EB in Human Monocytic Cells.
PG  - 1161
LID - 10.3389/fimmu.2017.01161 [doi]
LID - 1161
AB  - Aberrant activation of the innate immune system, including NOD-like receptor 
      pyrin domain containing 3 (NLRP3) inflammasome-dependent interleukin-1beta (IL-1beta) 
      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-1beta maturation in human monocytic cells. In this study, we 
      examined the underlying mechanisms of secreting IL-1beta during hyperglycemia, with 
      a focus on the alteration of Ca(2+) homeostasis and lysosomal exocytosis. We 
      found that high glucose (HG; 30 mM glucose for 48 h) altered Ca(2+) homeostasis 
      by reducing lysosomal Ca(2+) concentration that appeared to be resulted from 
      Ca(2+) moving out of lysosomes into cytosol in human monocytic cell lines, U937 
      and THP-1 cells. Moreover, HG-induced lysosomal Ca(2+)-dependent mature IL-1beta 
      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(2+) signals 
      through calcineurin/TFEB pathway, thus contributing to IL-1beta secretion in human 
      monocytic cells.
FAU - Tseng, Hisa Hui Ling
AU  - Tseng HHL
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau.
FAU - Vong, Chi Teng
AU  - Vong CT
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau.
FAU - Kwan, Yiu Wa
AU  - Kwan YW
AD  - Faculty of Medicine, School of Biomedical Sciences, The Chinese University of 
      Hong Kong, Shatin, Hong Kong.
FAU - Lee, Simon Ming-Yuen
AU  - Lee SM
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau.
FAU - Hoi, Maggie Pui Man
AU  - Hoi MPM
AD  - State Key Laboratory of Quality Research in Chinese Medicine, Institute of 
      Chinese Medical Sciences, University of Macau, Taipa, Macau.
LA  - eng
PT  - Journal Article
DEP - 20170915
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5609581
OTO - NOTNLM
OT  - Ca2+ homeostasis
OT  - high glucose
OT  - interleukin-1beta
OT  - lysosomal Ca2+
OT  - lysosomal exocytosis
OT  - monocytes
EDAT- 2017/10/04 06:00
MHDA- 2017/10/04 06:01
PMCR- 2017/01/01
CRDT- 2017/10/04 06:00
PHST- 2017/04/19 00:00 [received]
PHST- 2017/09/01 00:00 [accepted]
PHST- 2017/10/04 06:00 [entrez]
PHST- 2017/10/04 06:00 [pubmed]
PHST- 2017/10/04 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.01161 [doi]
PST - epublish
SO  - Front Immunol. 2017 Sep 15;8:1161. doi: 10.3389/fimmu.2017.01161. eCollection 
      2017.