PI3K gamma controls IL-17A expression and attenuates alveolar bone loss in an experimental periodontitis model

Author(s)

Franchin, Marcelo ; Taira, Thaise Mayumi ; Prado, Douglas da Silva ; Speck Hernandez, Cesar Augusto ; de Andrade, Fabio Bonifacio ; Abdalla, Henrique Ballassini ; Napimoga, Marcelo Henrique ; Cunha, Thiago Mattar ; Fukada, Sandra Yasuyo ; Rosalen, Pedro Luiz

• Document type: Journal article
• Source: Inflammation Research; v. 72, n. 1, p. 8-pg., 2022-11-04.

Abstract

Objective In this study, we investigated the modulatory effects of PI3K gamma on IL-17A expression and the progression of experimental periodontitis in vivo. Methods Ligature-induced periodontitis was developed around the first molar of mice. Animals were treated with anti-mouse IL-17A or IPI-549 (PI3K gamma inhibitor). In addition, PI3K gamma-deficient mice (PI3K gamma(-/-)) were used in the study. Alveolar bone loss was measured and real-time PCR of Il17a and Rankl genes was performed. A bioinformatics analysis was carried out using the Gene Set Enrichment Analysis computational tool. Results Nine days after ligature placement, alveolar bone loss scores were significantly increased, with upregulation of Il17a and Rankl genes in the gingival tissues. Treatment with anti-mouse IL-17A (100 mu g/mice) significantly attenuated alveolar bone loss. Mice with ligature-induced periodontitis treated with IPI-549 (3 mg/kg) or PI3K gamma(-/-) mice showed reduced alveolar bone loss and downregulation of Il17a and Rankl gene expression in the gingival tissues. Consistent with this, the bioinformatics analysis showed upregulation of IL17F, IL17A, IL17D, and STAT3 genes, as well as greater activation of IL-17 and PI3KCI pathways (upregulation of PIK3CG gene) in the gingival tissue of patients with periodontitis. Conclusion PI3K gamma plays an important role in modulating IL-17A expression and alveolar bone loss in vivo and can be considered a promising pathway for the management of periodontal disease and the development of new therapies. (AU)

• FAPESP's process: 17/09898-0 - Bioprospection of novel anti-inflammatory molecules from natural Brazilian native products
• Grantee: Pedro Luiz Rosalen
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/15563-9 - Characterization of new pharmacological targets and study of the activity of a 4-phenyl coumarin in the differentiation of Th17 lymphocytes in the development of periodontal disease
• Grantee: Marcelo Franchin
• Support Opportunities: Scholarships in Brazil - Post-Doctoral