The Role Of Neuregulin-1β In Mucus Hypersecretion Of Inflammatory Airway

Objective To investigate the role of neuregulin (NRG)1β in mucushypersecretion of inflammatory airway. Methods After stimulating theairway epithelial cells of line HBE16with IL-1β, NRG1β mRNA andmucin (MUC)5AC mRNA were detected by reverse transcriptionpolymerase chain reaction (RT-PCR), the protein of NRG1β and MUC5ACwas measured by ELISA, and phosphorylated erythroblastic leukemia viraloncogene homolog (ErbB)1, ErbB2, ErbB3, ErbB4were detected bywestern blotting. Pretreating the cells with antibody of ErbB1, ErbB2,ErbB3, ErbB4, inhibitors of p38mitogen-activated protein kinase (MAPK),ERK1/2, mitogen-and stress-activated protein kinase (MSK)1andantibody of cAMP-response element-binding protein (CREB), thenNRG1β was used as the stimulating factor, finally MUC5AC measured byELISA was compared with the group stimulated by NRG1β simply.Results IL-1β can increase markedly the level of NRG1β mRNA andMUC5AC mRNA, and also the protein of NRG1β and MUC5AC indose-dependent. NRG1β (concentration at1,10,100,200nmol/L) can also increase the expression of MUC5AC (0.328±0.055,0.364±0.086,0.650±0.134,0.586±0.068) compared with the control group(0.227±0.019), the result has significance of statistics (P<0.05). Theexpression of phosphorylated ErbB2and ErbB3stimulated by NRG1β ispositive, contrarily phosphorylated ErbB1and ErbB4are negative.Pretreating with antibody of ErbB2, ErbB3, inhibitors of p38MAPK,ERK1/2, MSK1and antibody of CREB, then sitmulating with NRG1β, theexpression of MUC5AC is reduced (0.221±0.033,0.238±0.044,0.386±0.021,0.352±0.022,0.294±0.017,0.252±0.019) compared withNRG1β group(0.650±0.134), the result has significance of statistics(P<0.05). Conclusion IL-1β causes airway hypersecreton probably viaNRG1β combining with ErbB2and ErbB3heterodimers, then activatingthe MAPK/MSK1/CREB signal conduct.