Autor(es)

da Silva Filho, Mario Brito ; Aniceto, Gabriela ; Fernandes, Patricia Maria ; Aquino, Iara Gonsalves ; Mendes, Gustavo Duarte ; Napimoga, Marcelo Henrique ; Clemente-Napimoga, Juliana Trindade ; Abdalla, Henrique Ballassini

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 252, p. 7-pg., 2024-11-23.

Resumo

Our previous studies have demonstrated the analgesic effects of botulinum toxin type A (BoNT/A) in a preclinical model of rheumatoid arthritis of the temporomandibular joint, where we proposed that BoNT/A decreases the neurogenic milieu after reaching the subnucleus caudalis. However, it is unknown whether BoNT/A directly regulates microglial cell activity. Therefore, the present study investigates the effects of BoNT/A on a microglial murine cell lineage (BV-2) in different inflammatory conditions. Cellular viability and proliferation were carried out with different concentrations of BoNT/A (ranging from 0.3125 to 20 U/mL) for 24 h. Cells were primed with carrageenan (300 mu g/mL) or Lipopolysaccharides (LPS) (20 ng/mL). The gene expression of IL-1 beta, IL-6, IL-18, TNF-alpha, Ikk beta, p65, Iba1 were quantified using PCR-RT. The supernatant was used to determine IL-1 beta, IL-6, and TNF-alpha levels. For all data, the significance level was set at 5%. Overall, data analysis revealed that BoNT/A 1.25 U/mL exhibited the greatest effect cell viability and proliferation. In addition, genes associated with inflammatory response in both stimuli (carrageenan and LPS) were downregulated in the presence of BoNT/ A. Lastly, BoNT/A mitigates the protein levels of IL-1 beta and TNF-alpha in a time and dose-dependent manner. In conclusion, our results revealed that BoNT/A directly modulates the microglial cells' activities in an inflammatory context, opening new perspectives for using BoNT/A, considering its potential immunomodulatory effect. (AU)

• Processo FAPESP: 17/22334-9 - Uso de sistemas de liberação de fármacos para o desenvolvimento e aplicabilidade de agentes anti-inflamatórios com potencial efeito imunomodulador e neuroprotetor
• Beneficiário: Marcelo Henrique Napimoga
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/22645-0 - Avaliação do impacto do inibidor da epóxi hidrolase solúvel, TPPU, na produção de mediadores lipídicos especializados pro-resolvinas como uma abordagem farmacológica para o tratamento de desordens inflamatórias
• Beneficiário: Henrique Ballassini Abdalla
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado