Vasoactive Intestinal Peptide Immunoregulatory Role at the Periapex: Associative and Mechanistic Evidences from Human and Experimental Periapical Lesions
| Autor: | André Petenuci Tabanez, Priscila Maria Colavite, Steven R. Little, Charles Sfeir, Jessica Lima Melchiades, Michelle de Campos Soriani Azevedo, Ana Paula Favaro Trombone, Carolina Favaro Francisconi, Thiago Pompermaier Garlet, Renato Menezes Silva, Gustavo Pompermaier Garlet |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Vasoactive intestinal peptide Periapical Granuloma Endogeny T-Lymphocytes Regulatory Proinflammatory cytokine Lesion 03 medical and health sciences Mice 0302 clinical medicine Immune system Osteoprotegerin medicine Animals Humans Receptor LINFÓCITOS T General Dentistry business.industry 030206 dentistry Mice Inbred C57BL 030104 developmental biology Immunology Th17 Cells medicine.symptom business hormones hormone substitutes and hormone antagonists Vasoactive Intestinal Peptide |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1878-3554 |
| Popis: | Introduction The balance between the host proinflammatory immune response and the counteracting anti-inflammatory and reparative responses supposedly determine the outcome of periapical lesions. In this scenario, the vasoactive intestinal peptide (VIP) may exert a protective role because of its prominent immunoregulatory capacity. In this study, we investigated (in a cause-and-effect manner) the potential involvement of VIP in the development of human and experimental periapical lesions. Methods Periapical granulomas (n = 124) and control samples (n = 48) were comparatively assessed for VIP and multiple immunologic/activity marker expression through real-time polymerase chain reaction. Experimental periapical lesions (C57Bl/6 wild-type mice) were evaluated regarding endogenous VIP expression correlation with lesion development and the effect of recombinant VIP therapy in lesion outcome. CCR4KO and IL4KO strains and anti-glucocorticoid-induced TNFR-related protein inhibition were used to test the involvement of Treg and Th2 cells in VIP-mediated effects. Results VIP expression was more prevalent in periapical granulomas than in controls, presenting a positive association with immunoregulatory factors and an inverse association/correlation with proinflammatory mediators and the receptor activator of nuclear factor kappa B ligand/osteoprotegerin ratio. Endogenous VIP expression up-regulation was temporally associated with lesion immunoregulation and a decline of bone loss. VIP therapy in mice prompted the arrest of lesion development, being associated with an anti-inflammatory and proreparative response that limits the proinflammatory, Th1, Th17, and osteoclastogenic response in the periapex. The VIP protective effect was dependent of Treg migration and activity and independent of interleukin 4. Conclusions Our results show that VIP overexpression in human and experimental periapical lesions is associated with lesion inactivity and that VIP therapy results in the attenuation of experimental lesion progression associated with the immunosuppressive response involving Treg cells. |
| Databáze: | OpenAIRE |
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