PMID- 36305000
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240228
IS  - 1662-5099 (Print)
IS  - 1662-5099 (Electronic)
IS  - 1662-5099 (Linking)
VI  - 15
DP  - 2022
TI  - Apoptosis-associated speck-like protein containing a CARD-mediated release of 
      matrix metalloproteinase 10 stimulates a change in microglia phenotype.
PG  - 976108
LID - 10.3389/fnmol.2022.976108 [doi]
LID - 976108
AB  - Inflammation contributes to amyloid-beta and tau pathology in Alzheimer's disease 
      (AD). Microglia facilitate an altered immune response that includes microgliosis, 
      upregulation of inflammasome proteins, and elevation of matrix-metalloproteinases 
      (MMPs). Studies of cerebrospinal fluid (CSF) and blood in dementia patients show 
      upregulation of two potential biomarkers of inflammation at the cellular level, 
      MMP10 and apoptosis-associated speck-like protein containing a CARD (ASC). 
      However, little is known about their relationship in the context of brain 
      inflammation. Therefore, we stimulated microglia cultures with purified insoluble 
      ASC speck aggregates and MMP10 to elucidate their role. We found that ASC specks 
      altered microglia shape and stimulated the release of MMP3 and MMP10. 
      Furthermore, MMP10 stimulated microglia released additional MMP10 along with the 
      inflammatory cytokines, tumor-necrosis factor-alpha (TNFalpha), Interleukin 6 (IL-6), and 
      CXCL1 CXC motif chemokine ligand 1 (CXCL1). A broad-spectrum MMP inhibitor, 
      GM6001, prevented TNFalpha release. With these results, we conclude that MMP10 and 
      ASC specks act on microglial cells to propagate inflammation.
CI  - Copyright (c) 2022 Sanchez, Bhaskar and Rosenberg.
FAU - Sanchez, Kathryn E
AU  - Sanchez KE
AD  - Center for Memory and Aging, University of New Mexico, Albuquerque, NM, United 
      States.
FAU - Bhaskar, Kiran
AU  - Bhaskar K
AD  - Department of Molecular Genetics and Microbiology, University of New Mexico, 
      Albuquerque, NM, United States.
AD  - Department of Neurology, University of New Mexico, Albuquerque, NM, United 
      States.
FAU - Rosenberg, Gary A
AU  - Rosenberg GA
AD  - Center for Memory and Aging, University of New Mexico, Albuquerque, NM, United 
      States.
AD  - Department of Neurology, University of New Mexico, Albuquerque, NM, United 
      States.
LA  - eng
GR  - R01 NS083704/NS/NINDS NIH HHS/United States
GR  - RF1 NS083704/NS/NINDS NIH HHS/United States
PT  - Journal Article
DEP - 20221011
PL  - Switzerland
TA  - Front Mol Neurosci
JT  - Frontiers in molecular neuroscience
JID - 101477914
PMC - PMC9595131
OTO - NOTNLM
OT  - apoptosis-associated speck like protein containing a CARD (ASC)
OT  - cytokine
OT  - inflammasome
OT  - matrix-metalloproteinase 10 (MMP10)
OT  - microglia
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/29 06:00
MHDA- 2022/10/29 06:01
PMCR- 2022/01/01
CRDT- 2022/10/28 03:03
PHST- 2022/06/23 00:00 [received]
PHST- 2022/09/05 00:00 [accepted]
PHST- 2022/10/28 03:03 [entrez]
PHST- 2022/10/29 06:00 [pubmed]
PHST- 2022/10/29 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fnmol.2022.976108 [doi]
PST - epublish
SO  - Front Mol Neurosci. 2022 Oct 11;15:976108. doi: 10.3389/fnmol.2022.976108. 
      eCollection 2022.