Secretory Functions of Macrophages in the Human Pancreatic Islet Are Regulated by Endogenous Purinergic Signaling.
Animals
Antigens, CD
/ genetics
Calcium
/ metabolism
Cytokines
Cytosol
/ chemistry
Diabetes Mellitus
/ metabolism
Down-Regulation
Gene Expression Regulation
Humans
Islets of Langerhans
/ cytology
Macrophages
/ physiology
Mice
Purines
/ metabolism
Receptors, Purinergic
/ metabolism
Signal Transduction
Transcriptome
Journal
Diabetes
ISSN: 1939-327X
Titre abrégé: Diabetes
Pays: United States
ID NLM: 0372763
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
12
07
2019
accepted:
26
03
2020
pubmed:
5
4
2020
medline:
23
10
2020
entrez:
5
4
2020
Statut:
ppublish
Résumé
Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. In this study, we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine interleukin-10 (IL-10) and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors are controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors MMP9 and IL-10 is reduced. We propose that in those states, exacerbated β-cell activity due to increased insulin demand and increased cell death produce high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity.
Identifiants
pubmed: 32245801
pii: db19-0687
doi: 10.2337/db19-0687
pmc: PMC7243286
doi:
Substances chimiques
Antigens, CD
0
Cytokines
0
Purines
0
Receptors, Purinergic
0
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1206-1218Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK111538
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK084321
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124527
Pays : United States
Organisme : NIDDK NIH HHS
ID : R21 DK114418
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK084321
Pays : United States
Organisme : NIDDK NIH HHS
ID : K01 DK111757
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK113093
Pays : United States
Organisme : NIEHS NIH HHS
ID : R33 ES025673
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK120456
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES025673
Pays : United States
Informations de copyright
© 2020 by the American Diabetes Association.
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