Hyperglycemia amplifies TLR-mediated inflammatory response of M(IL4) macrophages to dyslipidemic ligands.
J Leukoc Biol
; 116(1): 197-204, 2024 Jun 28.
Article
in En
| MEDLINE
| ID: mdl-38427690
ABSTRACT
Hyperglycemia is critical for initiation of diabetic vascular complications. We systemically addressed the role of hyperglycemia in the regulation of TLRs in primary human macrophages. Expression of TLRs (1-9) was examined in monocyte-derived M(NC), M(IFNγ), and M(IL4) differentiated in normoglycemic and hyperglycemic conditions. Hyperglycemia increased expression of TLR1 and TLR8 in M(NC), TLR2 and TLR6 in M(IFNγ), and TLR4 and TLR5 in M(IL4). The strongest effect of hyperglycemia in M(IL4) was the upregulation of the TLR4 gene and protein expression. Hyperglycemia amplified TLR4-mediated response of M(IL4) to lipopolysaccharide by significantly enhancing IL1ß and modestly suppressing IL10 production. In M(IL4), hyperglycemia in combination with synthetic triacylated lipopeptide (TLR1/TLR2 ligand) amplified expression of TLR4 and production of IL1ß. In summary, hyperglycemia enhanced the inflammatory potential of homeostatic, inflammatory, and healing macrophages by increasing specific profiles of TLRs. In combination with dyslipidemic ligands, hyperglycemia can stimulate a low-grade inflammatory program in healing macrophages supporting vascular diabetic complications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toll-Like Receptors
/
Hyperglycemia
/
Macrophages
Limits:
Humans
Language:
En
Journal:
J Leukoc Biol
Year:
2024
Document type:
Article
Affiliation country:
Germany
Country of publication:
United kingdom