ABSTRACT
Aim To investigate the effect of TAL and MAPK signal transduction on alveolar macrophage (AM) apoptosis and activity of chronic bronchitis (CB) rats.Methods CB model was established by BCG+LPS method and the in vitro and in vivo experiments were used. MTT method was used to detect the AM activity,and the apoptosis of AM was observed by electron microscope.Results The number of AM in BALF of CB rats was increased than that of normal group (P<0.01).The activity of AM was increased in model group than in control group.The apoptotic rate of AM in CB group was much lower than that in the control group [(13.93±3.34)% vs (5.37±1.38)%] (P<0.01).ERK inhibitor PD98059 induced the apoptosis of cultured AM while JNK inhibitor Curcumin reduced the apoptosis.TAL could inhibit ERK MAPK phosphorylation in AM of CB rats.Further investigation showed that Bcl-2 protein expression was significantly increased while Bax evidently decreased in AM of CB rats.TAL could significantly decrease Bcl-2 expression and increase Bax protein expression, which might be the mechanism of its effect.Conclusions There is an increased activity and decreased apoptosis of AM in CB rats compared with normal rats. TAL can inhibit AM activity and increase apoptosis of AM in CB rats which may be related to the therapeutic effect of CB. ERK and JNK MAPK signal transduction participates in the apoptosis of AM. Regulation of Bcl-2/Bax imbalance and MAPK phosphorylation in AM of CB rats might be the mechanism of its effect.
ABSTRACT
Aim To investigate the effect of MAPK signal transduction pathway on the expression of TNF-? in AM(alveolar macrophage) of CB(chronic bronchitis) rats,meanwhile,to initially discuss the possible regulated target of TAL(triterpene acids of loquat.leaf),to explain the mechanism about anti-inflammatory action of TAL on CB rats.Methods The depurated AM was incubated with the special inhibitors of MAPK signal transduction pathway respectively(ERK,p38 or JNK) and the expression of TNF-? was observed by RT-PCR and Western blot.Using factorial design,TNF-? level in AM culture supernatant was detected by ELISA.Results The special inhibitors of ERK(PD98059) and p38(SB203580) could change the expression of TNF-? in AM of CB rats apparently.Factorial analysis shows there is statistical significance between TAL,PD98059/SB203580 and mixture of them.Conclusions TAL reducing the expression of TNF-? may be related with the inhibition of ERK and p38 signal transduction pathway.It may be one of the mechanisms by which TAL has the preventive and therapeutic effects on chronic bronchitis.