Role of miRNA-155 in macrophage polarisation in stage III/IV periodontitis with type II diabetes mellitus: An analytical case-control study

Hum Immunol. 2024 Dec 11;86(1):111214. doi: 10.1016/j.humimm.2024.111214. Online ahead of print.

Abstract

Aim: To evaluate the role of miR-155 in macrophage polarisation in stage III/IV periodontitis with Type 2 diabetes mellitus (T2DM).

Materials and methods: Sixty four patients were recruited and categorized into Group I-systemically and Periodontally healthy (n = 16), Group II-systemically healthy with Stage III/IV Periodontitis(n = 16), Group III-Periodontally healthy with T2DM (n = 16) and Group IV- Stage III/IV Periodontitis with T2DM(n = 16).Gingival tissue samples were collected and Real time-PCR was carried out for microRNA-155, TNF- α(marker for M1 phenotype) and Arg-1(marker for M2 phenotype) gene expression.

Results: Group IV showed the highest increase in miR-155 fold change (FC) (11.17 ± 10.44), followed by groups III and II(10.35 ± 15.87, 5.1 ± 5.17 respectively) when compared to Group I. Likewise, the highest FC for TNF-α expression was observed in the group IV (10.11 ± 12.14). Groups II and III showed an almost similar increase in the FC(4.36 ± 4.48 and 4.79 ± 6.91, respectively). Periodontally healthy subjects demonstrated higher levels of Arg-1 gene expression(4.41 ± 5.17), followed by reduced expression in the groups II and IV (2.46 ± 2.21 and 2.65 ± 3.25, respectively). The TNF-α:Arg-1 ratio indicated that group I had higher Arg-1 expression, while group III and IV individuals had higher TNF-α expression. Compared to miR-155 and Arg-1, which demonstrated poor Area under the curve(AUC), sensitivity and specificity, TNF-α was able to distinguish between the groups III & IV (AUC = 0.74, p = 0.02, sensitivity 92 %, specificity 83 %, cut off = 27.28) and I & IV (AUC = 0.6, p = 0.03, sensitivity 81 %, specificity 77 %, cut off = 26.04).

Conclusion: Dysregulated miR-155 contributes to hyperinflammatory state in T2DM associated periodontitis by favouring macrophage polarisation towards the M1 phenotype.However, the strength of this relationship and the association with severity of periodontal disease could not be confirmed in this study.

Keywords: Arginase-1; Macrophage polarisation; Periodontitis; TNF-α,type 2 diabetes mellitus; miR-155.