Anexina A1 atenua alterações no perfil de fibroblastos sinoviais induzidas pela infecção do vírus chikungunya

• Ano de defesa: 2023
• Autor(a) principal: Gabrielly Carvalho de Mattos
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA; Programa de Pós-Graduação em Bioquímica e Imunologia; UFMG
• Palavras-chave em Português: Vírus Chikungunya; Fibroblastos; Artrite; Ligante RANK; Anexinas; Bioquímica e imunologia
• Link de acesso: http://hdl.handle.net/1843/64791

Chikungunya virus (CHIKV) causes an arthritogenic disease and exhibits a tropism for synovial fibroblastos (FLS), which are cells that contribute to the development of inflammatory arthritis, leading to pain and promoting the degradation of cartilage and bone. Considering the absence of CHIKV-specific drugs or vaccines, targeting synovial fibroblasts may be considered a therapeutic approach. Annexin A1 (ANXA1) is a protein with potent pro-resolving and analgesic effects, acting to reestablish tissue functionality. Hence, this work aims to explore the tibiofemoral joint during CHIKV infection and to assess the potential impact of ANXA1 on this process. To achieve this, C57BL/6 (wild-type) or BALB/c (wild-type and ANXA1-deficient) mice at 4 weeks of age were infected with an inoculum of 106 PFU of CHIKV in the paw. The C57BL/6 animal groups were treated with Ac2-26 (150 μg/mouse via i.p. or 10 μM/mouse via i.a.), and the tibiofemoral synovial tissue from C57BL/6 animals was collected to initiate primary culture of FLS. On the 3rd day post-infection (d.p.i.), ANXA1-deficient BALB/c mice infected with CHIKV exhibited more severe hyperplasia in the tibiofemoral synovial tissue compared to wild-type BALB/c infected mice, as indicated by histopathological scores. In infected C57BL/6 mice, there was an increase in the CD90-FAP+ FLS subpopulation in the synovial tissue, although all FLS populations analyzed showed increased RANKL expression after infection. In contrast, infected animals treated with Ac2-26 via i.p., initiated one hour before infection until the 6th d.p.i., had a reduction in the number of FLS as well as lower RANKL expression, resembling the profile of uninfected animals. Regarding treatment with Ac2-26 via i.a., administered at 3 hours post-infection (h.p.i.) and on the 3rd d.p.i., it was possible to identify a reduced nociceptive response until the 3rd d.p.i. in treated animals compared to untreated ones. Lastly, in vitro infection of FLS led to an increase in the cytokine IL-6 detected in the supernatant, as well as a decrease in cell viability, whereas in vitro treatment with the Ac2-26 peptide was able to decrease cytokine levels at 12 and 48 h.p.i. compared to infected and untreated wells. In conclusion, this study highlights that FLS are activated during CHIKV infection both in vivo and in vitro, and ANXA1 and Ac2-26 can control this activity, suggesting an alternative approach for controlling inflammation and tissue dysfunction caused by CHIKV.