A Study On Molecular Mechanism Of Airway Mucus Hypersecretion Induced By PM2.5

Objective To study on the main signal transduction mechanism ofairway mucus hypersecretion induced by PM2.5and clarify the role ofMAPK（ERK1/2、JNK、P38）pathway in airway mucus hypersecretioninduced by PM2.5.Methods This study was divided into three parts: experimentalsubjects were cell lines and rats in first part, while rats in second and thirdpart. According to experimental condition, subjects were divided intocontrol group, experimental group, treatment group. MTT assay was usedto detect the influence of PM2.5on the gowth of HBE16cell line. RT-PCR,ELISA and Western Blotting were respectively performed to detectexpression changes of MUC5AC, TNF-α, IL-1β and phosphorylation ofJNK、ERK1/2、P38MAPK on both transcription and translation level, whileElectrophoretic mobility shift assays (EMSA) to detect the DNA-bindingactivities of AP-1and NF-кB.Results The first part: MUC5AC expression on the transcription andtranslation level was significantly increased in lung tissue of rat（scomparedto control group，P＜0.05），which indicated that PM2.5could induceincreased expression level of p-JNK、p-ERK1/2、p-P38, and there is significant distinction in that of p-ERK1/2、p-P38（compared to controlgroup，P＜0.01). There was no significant distinction between PM2.5treating group and control group in HBE16cell line.TNF-αandIL-1βexpression level in rat lung tissue was highly increased（P＜0.05），but not in HBE16cell.The second part of our reseach indicated that specificinhibitor of ERK1/2and JNK could significantly down-regulate theexpression level of MUC5AC provoked by PM2.5when compared to theinhibitors against P38respectively (the experimental group compared withthe control group, P<0.05). he third part: the binding activity of the level ofNF-κ B, AP-1and the content of MUC5AC in lung tissue of rats hassignificant difference (P<0.05) after PM2.5stimulated.Conclusion1. PM2.5could induce airway mucus hypersecretion ondose-dependence.2. MAPK（ERK1\2、JNK、P38） pathway was involvedin PM2.5-induced airway mucus hypersecretion, relativity betweenERK1/2and PM2.5was highest, while JNK and PM2.5was less.3. Therewas a close relationship between transcription factor NF-кB、AP-1andMUC5AC.4. PM2.5can cause nonspecific inflammatory of airway in vivo,these inflammatory factors were important reason of airway mucushypersecretion condition worsening, and the results of in vivo comparedwith in vitro was also illustrates the complementary mechanism.