Pro-inflammatory effects of early non-enzymatic glycated proteins in human mesothelial cells vary with cell donor’s age

Abstract

Background and purpose: Diabetes mellitus is prevalent in the elderly population. It is also a disease causing tissue damage through several different mechanisms. Some of these mechanisms are also activated by ageing and this overlap raises questions about how diabetes induces damage in the elderly. Early products of non-enzymatic glycation of proteins (Amadori adducts), and the ageing process share the capacity to induce oxidative stress and inflammation in human peritoneal mesothelial cells (HPMCs). We have evaluated the interactions between the age of the donor of the HPMCs and the pro-inflammatory effects of Amadori adducts in those cells.

Experimental approach: HPMCs were isolated from 20 individuals (age range 21–81 years) and grown in culture. Using different experimental approaches we determined NF-κB dependent transcriptional activity and different NF-κB-related pro-inflammatory gene and protein expressions in basal (or non-stimulated) conditions and after stimulation with two Amadori adducts; highly-glycated haemoglobin and glycated bovine serum albumin.

Key results: Amadori-induced effects on NF-κB dependent-transcription and on the activity of NOS, COX and several NF-κB-related pro-inflammatory genes (iNOS, COX-2, TNF-α, IL-1β, and IL6) diminished as the donor's age increased, being practically absent in cells from donors more than 65 years old. Such decreased effects were inversely correlated with an increased basal expression and activity of these pro-inflammatory markers with age.

Conclusions and implications: Pro-inflammatory effects of Amadori-adducts in HPMCs were strongly dependent on cell donor's age. This may have significant implications for the mechanisms underlying diabetes-induced tissue damage in patients of different ages.s.