P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

Abstract

Chronic inflammation plays a major role in development of type 2 diabetes mellitus (T2DM). C-reactive protein (CRP) and inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) are directly involved in the occurrence of insulin resistance. Increased extracellular ATP levels can amplify the inflammatory response in vivo via the P2X7 receptor. The present study aimed to assess the relationship between P2X7 receptor expression in human peripheral blood monocytes and plasma levels of TNF-α, IL-1β, and CRP in T2DM patients. The results showed the association of increased P2X7 receptor expression of monocytes with high serum CRP, TNF-α, and IL-1β levels. TNF-α and IL-1β levels were lowest in healthy subjects; in T2DM patients, these inflammatory markers were less abundant in individuals with normal CRP levels compared to those with high CRP contents. In contrast, IL-10 levels in T2DM patients with high CRP levels were dramatically decreased. P2X7 receptor expression in monocytes from T2DM patients with high CRP levels was significantly increased in comparison with healthy individuals and T2DM patients with normal CRP levels. These findings indicated that P2X7 receptor in peripheral blood monocytes may be involved in the pathological changes of T2DM, particularly affecting patients with high CRP levels.

Changes of Regulatory T Cells and of Proinflammatory and Immunosuppressive Cytokines in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

“…Previous studies suggested that IL-10 could suppress the proliferation of T leukomonocyte and the secretion of cytokines [ 121 ], whereas TGF- β may sustain the expression of Foxp3 in CD4 + CD25 + Treg to enhance immunosuppressive function [ 122 , 123 ]. Consistent with our findings, several studies have shown a significantly decreased level of serum IL-10 in T2DM patients [ 88 , 124 ]. Correlation of T2DM with Treg cells and TGF- β is generally negative [ 116 ].…”

LncRNA uc.48+ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264.7 macrophages

“…The experiments in the present study showed that the mRNA and protein expression of P2X 7 R in RAW264.7 cells were increased due to high glucose and high FFA treatment, compared with those in the controls. This was similar to the results of our preliminary investigation (6,27), which showed that the P2X 7 R may alter the innate immune system contributing to the development of T2DM. The present study was limited by the fact that no binding assays were performed to examine the binding of ATP to P2X 7 R. Future investigations aim to improve on this aspect of the pilot study.…”

“…The events leading to T2dM are complex, however, emerging evidence has shown that various purinergic signaling components may be important regulatory factors (20,21). Our previous preliminary study demonstrated that P2X 7 R in peripheral blood monocytes may be involved in the pathological changes of T2dM, particularly affecting patients with high CRP levels (6). In the previous study, it was found that the expression of uc.48+ in the serum of patients with T2DM and in RAW264.7 macrophages treated with high glucose and high FFAs was significantly increased, compared with the expression in the healthy individuals and control group, respectively.…”

“…By contrast, monocytes/macrophages are important in the occurrence and development of T2dM, which is regarded as a type of low-grade inflammation (4,5). In our previous study, it was demonstrated that the increased expression of P2X 7 receptor (P2X 7 R) in peripheral blood monocytes may alter the innate immune system, contributing to the development of T2DM (6). The high plasma FFA levels in the inflammatory condition of T2dM may result in the continuous secretion of intracellular ATP, which causes the accumulation of extracellular ATP (7).…”

Purinergic Signaling in the Cardiovascular System

“…P2X7 receptors on monocytes may be involved in the pathological changes of type 2 diabetes mellitus, particularly in patients with high C-reactive protein levels. 204 Up 4 A is a vessel constrictor and is associated with diabetes mellitus. 205 Adenosine-insulin signaling in fetoplacental endothelial dysfunction in gestational diabetes mellitus has been reviewed.…”