M1 and M2 macrophages markers are alternately expressed during periapical lesion development

Abstract

Objectives The present study evaluated the phenotypic characterization of M1 and M2 macrophage subtypes during the development of periapical lesion (PL). Materials and Methods PL was induced in the lower first molars of 96 mice. After the experimental periods of 2, 7, 14, 21, and 42 days, the animals were euthanized and the jaws were dissected and submitted to the following analyzes: microscopic descriptive analysis and fluorescence microscopy morphometry of PL size (mm²); quantitative gene expression analysis by qRT-PCR for M1 (Cxcl10, CxCL9, and Nos2) and M2 phenotypes ((Arg1, Fizz1, Ym1, and Mrc1); and M1- (GM-CSF, IFN-g, IL-6, IL-1β, TNF-α) and M2- ((IL-4, IL-13, and IL- 10) related cytokines quantification by Luminex. Data were statistically compared by ANOVA, Tukey post-test, Kruskal-Wallis and Dunn post-test (α = 5%). Results PL area and inflammatory infiltrate increased over experimental periods. By a contextual view, it could be observed a pro-inflammatory profile and a higher activation of M1 phenotype markers in the initial periods of 2 and 7 days. At 21 day time point, microscopic features and M2 subtype predominance indicated a repair attempt. However, at 42 days, an exacerbation of immunoinflammatory process and return to the M1 macrophage profile were evidenced. Conclusion M1 and M2 macrophage polarization related markers were expressed alternately during the dynamic progression of the PL. Clinical Relevance: This study provides a deeper understanding about M1 and M2 macrophages participation on development, progression, and outcome of PL, as well as guides possible therapeutic targets.