Apical periodontitis promotes insulin resistance and alters adaptive immunity markers in rats

Renato Felipe Pereira; Gestter Willian Lattari Tessarin; Fernando Yamamoto Chiba; Maria Sara de Lima Coutinho Mattera; Amanda Gomes Pereira; Thais Verônica Saori Tsosura; Victor Gustavo Balera Brito; Renan Akira Fujii de Oliveira; Edilson Ervolino; Sandra Helena Penha de Oliveira; Luciano Tavares Angelo Cintra; Doris Hissako Matsushita

doi:10.1016/j.sdentj.2021.07.005

Apical periodontitis promotes insulin resistance and alters adaptive immunity markers in rats

Saudi Dent J. 2021 Dec;33(8):979-986. doi: 10.1016/j.sdentj.2021.07.005. Epub 2021 Jul 14.

Authors

Renato Felipe Pereira¹, Gestter Willian Lattari Tessarin^{2

3}, Fernando Yamamoto Chiba⁴, Maria Sara de Lima Coutinho Mattera¹, Amanda Gomes Pereira⁵, Thais Verônica Saori Tsosura¹, Victor Gustavo Balera Brito¹, Renan Akira Fujii de Oliveira⁴, Edilson Ervolino^{2

6}, Sandra Helena Penha de Oliveira¹, Luciano Tavares Angelo Cintra⁴, Doris Hissako Matsushita^{1

2}

Affiliations

¹ Programa de Pós-graduação Multicêntrico em Ciências Fisiológicas, PPGMCF, SBFis, São Paulo State University (UNESP), School of Dentistry, Araçatuba, São Paulo, Brazil.
² Department of Basic Sciences, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
³ University Center North Paulista (UNORP), São José do Rio Preto, SP, Brazil.
⁴ Department of Preventive and Restorative Dentistry, São Paulo State University (UNESP), School of Dentistry, Araçatuba, SP, Brazil.
⁵ Internal Medicine Department, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, Brazil.
⁶ Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, SP, Brazil.

Abstract

Objective: Apical periodontitis (AP) is a chronic or acute inflammatory disease usually developed from endodontic infections, predominantly due to gram-negative anaerobic bacteria invading the dental pulp. This study aimed to evaluate lymphocyte markers to assess the involvement of adaptive immunity in insulin resistance (IR) in a rat model of AP.Design.Forty-five male Wistar albino rats were divided into 3 groups (control, 1AP and 4AP). AP was induced in the upper right first molar (1AP), and in the first and second upper and lower right molars (4AP). The spleen was collected to evaluate the expression of transcription factors involved in lymphocyte polarization, including T-bet (Th1), GATA3 (Th2), and FOXP3 (Treg). Blood samples were assessed for serum cytokine levels transcribed by the respective lymphocyte polarizations, INF-γ (Th1), IL-4 (Th2) and TGF-β (Treg). In addition, glucose and insulin levels were measured to evaluate IR by the HOMA-IR method.

Results: The results showed higher T-bet expression on AP groups, along with lower GATA3 and FOXP3 expression in the 1AP, in addition to increased GATA3 and decreased FOXP3 expression in the 4AP group compared to the CN group. There was no difference in the INF-γ levels, while IL-4 was decreased in the AP groups. Taken together, these results suggest that the adaptive immune system, with a predominance of the Th1 polarization, may be involved in the development of IR in rats with AP.

Conclusions: AP promotes increase in the expression of T-bet (4AP) and decrease of FOXP3 expressions and IL-4 levels (1AP and 4AP). However, depending on the number of lesions (1 or 4 lesions), the expression of GATA3 appears differently. Thus, innate immunity and adaptive immunity may contribute to the IR observed in rats with AP.

Keywords: 1AP, group with 1 apical periodontitis; 4AP, group with 4 apical periodontitis (4AP); AP, Apical periodontitis; Adaptive immunity; Apical periodontitis; Endodontics; FOXP3, forkhead box P3; GATA3, Binding protein 3; IL-4, interleukin-4; INF-γ, Interferon-gamma; IR, Insulin resistance; Insulin resistance; T-bet, T-box transcription factor TBX21; TGF-β, Transforming growth factor beta; Th1, T helper 1; Th2, T helper 2; Treg, Regulatory T cell.