1 型糖尿病患者唾液巨噬细胞激活相关趋化因子和丝裂原活化蛋白激酶激酶降解蛋白酶活性。

Salivary macrophage activation-related chemokines and mitogen-activated kinase kinase-degrading proteolytic activity in type 1 diabetes mellitus.

机构信息

Department of Periodontology, Institute of Dentistry, University of Turku, Turku, Finland.

Department of Pediatric Dentistry, Faculty of Dentistry, Sakarya University, Sakarya, Turkey.

出版信息

J Periodontol. 2023 Jul;94(7):896-904. doi: 10.1002/JPER.22-0314. Epub 2023 Jan 30.

DOI:10.1002/JPER.22-0314

PMID:36601897

Abstract

BACKGROUND

This cross-sectional study aimed to evaluate salivary concentrations of macrophage activation-related chemokines and mitogen-activated kinase kinase (MAPKK)-degrading proteolytic activity in children and adolescents with and without type 1 diabetes mellitus (T1DM).

METHODS

A total of 122 children and adolescents (65 T1DM patients, 50.8% female, mean age:10.9 years; 57 systemically healthy controls, 36.8% female, mean age: 9.5 years) were included in the study. Salivary concentrations of interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-2, MCP-3, MCP-4, macrophage-derived chemokine (MDC), macrophage migration inhibitory factor (MIF), monokine induced by interferon gamma (MIG), and macrophage inflammatory protein-1 alpha (MIP-1α) were quantified using a bead-based technique. MAPKK-degrading proteolytic activity was detected using fluorescent peptide substrates.

RESULTS

The T1DM group had higher plaque index (PI%, p = 0.032) and bleeding on probing (BOP%, p = 0.045) scores, and lower decayed, missing, filled teeth (dmft/DMFT, p = 0.002) index scores compared to the healthy controls. Compared to the controls, salivary MCP-1 (p = 0.007), MCP-3 (p < 0.001), MIG (p = 0.007), and MIP-1α (p = 0.033) concentrations were elevated whereas MCP-4 concentrations decreased (p < 0.001) in the T1DM group. After adjusting for age, PI%, BOP%, and dmft/DMFT scores, significant differences in salivary concentrations of MIG (p = 0.033) and MIP-1α (p = 0.017) were observed between the groups. Moreover, protease activities directed to the cleavage sites of MEK23-18 (p = 0.001), MKK6b7-22 (p = 0.007), MKK451-66 (p = 0.005), MKK7b37-52 (p = 0.034), and MKK7b69-84 (p = 0.009) were elevated in the T1DM group.

CONCLUSION

T1DM disrupts the salivary macrophage activation-related chemokine profile and dysregulates proteolytic MAPKK cleavage. These findings can be an outcome of the impaired systemic immune response in T1DM.

摘要

背景

本横断面研究旨在评估伴有和不伴有 1 型糖尿病（T1DM）的儿童和青少年唾液中巨噬细胞激活相关趋化因子浓度和丝裂原活化蛋白激酶激酶（MAPKK）降解蛋白水解活性。

方法

共纳入 122 名儿童和青少年（65 名 T1DM 患者，女性占 50.8%，平均年龄 10.9 岁；57 名系统性健康对照者，女性占 36.8%，平均年龄 9.5 岁）。使用基于珠子的技术定量检测干扰素γ诱导蛋白-10（IP-10）、单核细胞趋化蛋白（MCP）-1、MCP-2、MCP-3、MCP-4、巨噬细胞衍生趋化因子（MDC）、巨噬细胞迁移抑制因子（MIF）、γ干扰素诱导的单核因子（MIG）和巨噬细胞炎性蛋白-1α（MIP-1α）的浓度。使用荧光肽底物检测 MAPKK 降解蛋白水解活性。

结果

与健康对照组相比，T1DM 组的菌斑指数（PI%，p=0.032）和探诊出血（BOP%，p=0.045）评分较高，而龋齿、缺失、补牙（dmft/DMFT，p=0.002）指数评分较低。与对照组相比，T1DM 组唾液中 MCP-1（p=0.007）、MCP-3（p<0.001）、MIG（p=0.007）和 MIP-1α（p=0.033）浓度升高，而 MCP-4 浓度降低（p<0.001）。在调整年龄、PI%、BOP%和 dmft/DMFT 评分后，两组间 MIG（p=0.033）和 MIP-1α（p=0.017）的浓度仍存在显著差异。此外，T1DM 组中 MEK23-18（p=0.001）、MKK6b7-22（p=0.007）、MKK451-66（p=0.005）、MKK7b37-52（p=0.034）和 MKK7b69-84（p=0.009）切割位点的蛋白酶活性升高。