Interleukin 33 /ST2 axis and galectin-3 in the pathogenesis of experimental periapical lesions.

Immunopathological processes play an important role in the pathogenesis of periapical lesions. Previous studies in animal models and human tissue, including our own have established that immunomodulatory cytokines produced mainly by T cells and accessory cells correlate with cellular composition at different phases of lesion development. It has ben recently established that galectins and IL33/ST2 axis significantly influence inflammatory processes in different pathological conditions in experimental models of human diseases. However, their possible roles in the initiation and expression of periapical lesions are completely unknown. We plan to analyze the roles of these elements of innate response by complementary approaches using ST2 (IL33 receptor) genetically deficient mice and recombinant IL33 and galectin-3 knockout mice and newly synthesized inhibitor of galectin-3. Using experimental model of periapical lesion in mice to study the effect of ST2 and galectin-3 deletion in granuloma development evaluated by histology and immunohistochemistry, cellular make up of the lesion using flow cytometry and cytokine expression production by RT-PCR and ELISA assays. Additionally, we will test the capacity of IL33 and galectin inhibitor to modulate granuloma development in “wild type” BALB/c and C57Bl/6 mice. Taken together, these experiments should contribute to our understanding of multifactorial events in the development of periapical lesions.