The role of interleuki-17 and -33 in the immunopatogenesis of human and experimental chronic periapical lesions

Abstract

Chronic periapical lesions are a sequel of bacterial infection of pulpar and endodontic environment, which results in inflammation and destruction of periradicular tissues. Although the presence of pathogenic microflora is necessary to trigger the development of periapical disease, the progress and the severity of this process are highly dependent on host's immune and inflammatory responses to bacteria and their antigens. Therefore, the knowledge of cytokines immunobiology is essencial to reach effective therapies to control immunoinflammatory diseases characterized by tissue destruction as in periapical lesions. For this purpose, samples of human and experimental chronic periapical lesions will be used to identify and to correlate the expression of interleukin -17 (IL-17) and -33 (IL-33), cytokines deeply involved in host's immune and inflammatory responses to the bacterial infection, to other inflammatory cytokines and osteclastogenic factors involved in periapical lesions progression. While human granulomas (N=57) and control tissue (N=40) will be obtained from a samples bank of this research group, the experimental lesions will be induced in wild-type and knock-out (KO) mice by pulpal exposure and bacterial contamination. Gene expression of cytokines and chemokines (IL-17A, Il-17F, IL-6, IL-23, IL-33, IL-1beta, TNF-alpha, IFN-gamma, IL-10, IL-4) as well as, osteoclastogenic factors (RANKL and OPG) will be assed using reverse transcriptase polymerase chain reactions. In addition, samples of experimental lesions will be prepared for light microscopic examination, morphometric and TRAP-analyses. In this way, the role of IL-17 and IL-33 on the development of periradicular diseases and the mechanisms involved in their regulation might be assessed. Certainly, a better understanding of the immunopathogenesis of periapical lesions will contribute to improve new therapies to the diagnosis and clinical procedures of these pathologies. (AU)