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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF ENDODONTICS; v. 45, n. 10, p. 1228-1236, OCT 2019.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 15/25618-2 - VIP (vasoactive intestinal peptide) and PACAP (pituitary adenylate cyclase-activating polypeptide) roles in M2 polarization and their impact on the alveolar bone repair process
• Grantee: Michelle de Campos Soriani Azevedo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/24637-3 - MSCs and m2 as determinants of the constructive or destructive nature of inflammatory microenvironments associated with bone tissue
• Grantee: Gustavo Pompermaier Garlet
• Support Opportunities: Research Projects - Thematic Grants