RESUMO
Toxic inflammatory response is frequently introduced upon virus infection. In this study, RAW264.7 cells were infected with porcine circovirus type 2 (PCV2) and treated with Sargassum polysaccharide SP. It was found that PCV2 infection induced increased significant inflammation response represented with increased secretion of inflammatory cytokines, corresponding with promoted HAT activity, inhibited HDAC activity, elevated HDAC1 mRNA levels, and up-regulated acetylation levels of H3 and H4 in RAW264.7 cells. SP treatment significantly inhibited the increase of inflammatory cytokines, HAT activity and the acetylation of histones, but dramatically increased the HDAC activity and the expression of HDAC1. From these results, SP might be able to protect immune cells from virus induced damages through inhibiting the inflammatory responds by maintaining an equilibrium between the activity of HATs and HDACs which contributes to an appropriate level of histone acetylation.
Assuntos
Anti-Inflamatórios/farmacologia , Circovirus/fisiologia , Histonas/metabolismo , Polissacarídeos/farmacologia , Sargassum/química , Acetilação/efeitos dos fármacos , Animais , Citocinas/genética , Camundongos , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
In the present study, effect of Sophora subprosrate polysaccharide on PCV2 infection-induced inflammation and histone acetylation modification in swine alveolar macrophage 3D4/2 cells was described for the first time. The relationship between histone acetylation modifications and inflammation response was investigated. The results showed that PCV2 infection induced inflammation by promoting the secretion of TNF-α, IL-1ß, IL-6 and IL-10 in 3D4/2 cells. The production of TNF-α, IL-1ß and IL-6 and their mRNA expression levels markedly decreased while the level and mRNA expression of IL-10 were elevated when the cells were treated with Sophora subprosrate polysaccharide. The SSP also decreased the activity of HATs, histone H3 acetylation (Ac-H3) and histone H4 acetylation (Ac-H4), p65 phosphorylation (P-p65) in the cells infected with PCV2 while HDACs activity was down-regulated, which involved in the inhibitory effect of SSP on histone acetylation and NF-κB signaling pathways activation. Down-regulation of HAT1 mRNA expression and up-regulation of HDAC1 mRNA expression further support the inhibitory effect of SSP on histone acetylation. In conclusion, Sophora subprosrate polysaccharide antagonized inflammatory responses induced by PCV2, via mechanisms involved in histone acetylation and NF-κB signaling pathways.