Vasoactive Intestinal Peptide Immunoregulatory Role at the Periapex: Associative and Mechanistic Evidences from Human and Experimental Periapical Lesions

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Soriani Azevedo, Michelle de Campos ^[1] ; Garlet, Thiago Pompermaier ^[2] ; Francisconi, Carolina Favaro ^[1] ; Colavite, Priscila Maria ^[1] ; Tabanez, Andre Petenuci ^[1] ; Melchiades, Jessica Lima ^[1] ; Favaro Trombone, Ana Paula ^[3] ; Sfeir, Charles ^{[4, 5, 6]} ; Little, Steven ^{[4, 7]} ; Silva, Renato Menezes ^[8] ; Garlet, Gustavo Pompermaier ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Dent Bauru, Dept Biol Sci, Bauru, SP - Brazil

^[2] Univ Estadual Ponta Grossa, Dept Struct & Mol Biol & Genet, Ponta Grossa, Parana - Brazil

^[3] Univ Sagrad Coragao, Bauru, SP - Brazil

^[4] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA - USA

^[5] Univ Pittsburgh, Ctr Craniofacial Regenerat, Pittsburgh, PA - USA

^[6] Univ Pittsburgh, Sch Dent Med, Dept Periodont & Prevent Dent, Pittsburgh, PA - USA

^[7] Univ Pittsburgh, Dept Chem & Petr Engn, Pittsburgh, PA - USA

^[8] Univ Texas Hlth Sci Ctr Houston, Sch Dent, Dept Endodont, Houston, TX 77030 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF ENDODONTICS; v. 45, n. 10, p. 1228-1236, OCT 2019.
• Citações Web of Science: 1

Resumo

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 (C57BI/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. (AU)

• Processo FAPESP: 15/25618-2 - Papel de VIP (vasoactive intestinal peptide) e PACAP (pituitary adenylate cyclase-activating polypeptide)na polarização M2 e seu impacto no processo de reparo ósseo alveolar
• Beneficiário: Michelle de Campos Soriani Azevedo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/24637-3 - MSCs e M2 como determinantes da natureza construtiva ou destrutiva de microambientes inflamatórios associados ao tecido ósseo
• Beneficiário: Gustavo Pompermaier Garlet
• Modalidade de apoio: Auxílio à Pesquisa - Temático