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

Abstract

AbstractBackgroundThis 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).MethodsA 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.ResultsThe 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.ConclusionT1DM 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.