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Role of CCR5 in apical periodontitis etiopathogenesis

Abstract

Interest in the study of the CC 5 (CCR5) chemokine receptor has increased since it is involved not only in the infection of the organism and migration of leukocytes to sites of inflammation but also in cell signaling, including osteoblasts and osteoclasts, and currently plays a therapeutic role In various human diseases. However, the role of CCR5 in the protection or stimulation of tissue resorption associated with apical periodontitis has not yet been elucidated. The present research project proposes to characterize the involvement of CCR5 in the genesis and progression of apical periodontitis, using animals deficient for this molecule. Experimental induction of periapical lesions will be performed in CCR5 -/- (knockout) or wild type transgenic mice through the coronary opening of the lower 1st molars and exposure of the root canals to the oral environment for their contamination. After the death of the animals (at 0, 7, 21 and 42 days), the samples obtained in different experimental periods will be evaluated by conventional microscopy and fluorescence (morphometry and characterization of the lesions), histoenzimologia (TRAP for osteoclasts), immunohistochemistry, Immunofluorescence and real-time PCR, to characterize the inflammatory cell profile in the presence or absence of CCR5 (neutrophils, macrophages and CD4 and CD8 lymphocytes), expression of cytokines (IL-1±, TNF-±, IFN-³, IL 4, IL-6 and IL-10), their ligands (RANTES and MIP-1±) and factors involved in bone formation and resorption (RUNX2, NFATc1, ALP, RANK, RANKL, OPG and cathepsin K) and infection of tissues. It is hoped to characterize the role of CCR5 in apical periodontitis and, in the future, to apply molecular treatments directed to the silencing of this cell signaling pathway, as is currently the case in several inflammatory diseases, including periodontal disease. (AU)