Effect Of Histone Deacetylases On MAPK/NF-kB Pathway In Bronchial Asthmatic Mice

NTRODUCTION: A mouse model of bronchial asthma was induced by OVA induction and treated with histone deacetylase inhibitor(HDACI)Givinostat,histone deacetylase 6inhibitor(HDAC6I)Tubastatin A HCl and 8 inhibitor(HDAC8I)PCI-34051 to study the effects of different histone deacetylases on the MAPK pathway and NF-kB pathway in asthmatic mice and provide new ideas for the control,treatment and prognosis of asthma.Methods: Thirty-six female Bal b/c mice(normal 6-8 weeks old)were randomly divided into normal group(NS group),asthma group(AS group),dexamethasone group(DEX group),HDACI treatment group(GI group),HDAC6 I treatment group(TA group),HDAC8 I treatment group(PCI group).Except for the normal control group,the other 5groups were sensitized with ovalbumin OVA(20?g)and aluminum hydroxide gel(2mg)orally on day 0,day 7 and day 14,respectively.The normal control group was sensitized with an equal amount of physiology Saline for sensitization.Seven days after the last sensitization,the mice were started to be placed in a closed box and subjected to atomization with OVA(20mg/ml)using an ultrasonic nebulizer(3ml/min).NS group with the same amount of saline instead of OVA line excitation treatment.The GI group was orally administered 30 minutes before each challenge test,DEX,TA,PCI three groups to intraperitoneal injection.24 h after the last challenge test mice in each group airway responsiveness.The mice were sacrificed and paraffin sections of lung tissue were obtained.The hematoxylin-eosin(HE)staining was performed.The morphological changes of lung tissue and infiltration of inflammatory cells were observed under light microscope.The expression of ERK,JNK,p38,p65,p-ERK,p-JNK,p-p38,p-p65 protein in lung tissue of each group was detected by Western blotting.Results: Compared with the asthma group,three HDACI groups inhibited the airway responsiveness and inflammatory cell infiltration in the asthmatic mice.Compared with the normal group,the expression of p-ERK,p-JNK,p-p38 and p-p65 Asthma model group was significantly higher than the control group(p<0.05);these phosphorylation protein expression in the GI group,TA group and PCI group was significantly lower than the asthma group(p<0.05);GI group and TA group protein expression difference(p<0.05).However,the expression of phosphorylated protein in PCI group was significantlylower than that in GI and TA groups(p<0.05).Dexamethasone treatment group was able to inhibit OVA induced p38,ERK,JNK protein.The level of p-p65 in the asthma group was significantly higher than that in the normal group(p<0.05).The phosphorylation of p65 in HDAC8 I group was significantly inhibited compared with the asthma group(p<0.05),but the inhibition of protein expression in the GI and TA groups was not significantly different from that of the HDAC8 I group.Conclusion: Histone deacetylase may control the level of inflammatory cytokines by affecting the MAPK / NF-kB pathway,eventually leading to airway inflammatory cell infiltration and increasing airway inflammatory response in asthmatic mice.