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

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 age10.9 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.