Protective Role Of Sodium Butyrate Against Mycobacterium Bovis Infection Of Host

Tuberculosis(TB)is a chronic zoonotic disease that leads to 10 million humans and 50 million bovine tuberculosis cases every year worldwide.It poses a serious threat to public health and animal husbandry practices.TB is mainly caused by Mycobacterium tuberculosis(M.tuberculosis)and Mycobacterium bovis(M.bovis).After enter into macrophages,M.bovis can survive in the macrophages by inhibiting the immune mechanism by their own virulence factors thereby leading to immune evasion.In the process of interaction between macrophages and M.bovis,various host cells immune mechanisms including the regulation of histone acetylation play a critical role.In this study,we investigated the effects of sodium butyrate(NaB),a histone deacetylase inhibitor,in vivo and vitro and provided new insights and theoretical basis for exploring the pathogenesis of TB and the development of new drugs.The findings of the current study are as follows:1.In order to investigate the effect of sodium butyrate on THP-1 cells against M.bovis,this experiment used M.bovis to infect THP-1 cells for 3 h,and then removed extracellular.bovis and treated with sodium butyrate,0.5mM and 1.OmM,for 24 hours.Total protein,nuclear and cytoplasmic proteins were extracted.Total RNA and culture supernatants were also collected for further experiments.At the same time,CFU assay was also carried out.The expression of LL37,HDAC1,HDAC2,HDAC3,P-I?B?,I?B?,P65 and P-P65 was detected by Western blot.The results showed that sodium butyrate could promote the expression of LL37,histone acetylation and cell apoptosis and it inhibited the expression of HDAC1,HDAC2,HDAC3 and NF?B signaling pathway.Moreover,sodium butyrate treatment reduced the secretion of IL-1? and TNF-? in THP-1 cells after M.bovis infection and enhanced the ability of THP-1 cells to scavenge the intracellular M bovis.2.In order to study in vivo protective effects of sodium butyrate,C57BL/6 mice were treated with sodium butyrate before and after infection with.bovis.Sodium butyrate was injected intraperitoneally on every alternate day.Then,survival rate and body weight of the mice,pathological changes of the various organs,pulmonary CFU,pulmonary cellular aggregations and serum cytokine levels were investigated.The results showed that sodium butyrate 500 mg/kg treatment of the M.bovis infected mice significantly lowered the bacterial burden in the lungs as compared to untreated group.Similarly,the aggregation of inflammatory cells and the pathological changes in lungs of sodium butyrate treated mice were also lower as compared to untreated controls.Taken together,this study demonstrates that sodium butyrate,a histone deacetylase inhibitor,can enhance the clearance of M bovis in vivo and vitro suggesting that the regulation of histone acetylation could affect the host's resistance to M.bovis.Thus,the study provides an idea for the research and development of new anti-tuberculosis drugs.