[Role of neuregulin-1β in airway hypersecretion induced by in interleukin-1β]

To explore the role of neuregulin 1β (NRG-1β) in airway hypersecretion induced by interleukin (IL)-1β.

After stimulating the airway epithelial cell line HBE16 with IL-1β, the expressions of NRG-1β mRNA and mucin (MUC) 5AC mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), the proteins of NRG-1β and MUC5AC measured by enzyme-linked immunosorbent assay (ELISA) and phosphorylated erythroblastic leukemia viral oncogene homolog (ErbB)1-4 detected by Western blot. The cells were pre-treated with antibodies of ErbB1-4, inhibitors of p38 mitogen-activated protein kinase (MAPK), ERK1/2, mitogen- and stress-activated protein kinase (MSK)1 and antibody of cAMP-response element-binding protein (CREB). After the addition of stimulant NRG-1β, MUC5AC was measured by ELISA.

IL-1β could increase markedly the levels of NRG-1β mRNA and MUC5AC mRNA and also the proteins of NRG-1β and MUC5AC in a dose-dependent fashion. NRG-1β at concentrations of 1, 10, 100, 200 nmol/L increased the expression of MUC5AC (0.328 ± 0.055, 0.364 ± 0.086, 0.650 ± 0.134, 0.586 ± 0.068) versus the control group (0.227 ± 0.019). And the results had statistical significances (P < 0.05). The expressions of phosphorylated ErbB2 and ErbB3 stimulated by NRG-1β were positive while those of phosphorylated ErbB1 and ErbB 4 negative. After a pretreatment of antibodies of ErbB2, ErbB3, inhibitors of p38MAPK, ERK1/2, MSK1 and antibody of CREB and a stimulation of NRG-1β, the expression of MUC5AC decreased (0.221 ± 0.033, 0.238 ± 0.044, 0.386 ± 0.021, 0.352 ± 0.022, 0.294 ± 0.017, 0.252 ± 0.019) versus the NRG-1β group (0.650 ± 0.134). And the results had statistical significances (P < 0.05).

IL-1β may cause airway hypersecretion probably through the combination of NRG-1β with ErbB2 and ErbB3 heterodimers and the activation of MAPK/MSK1/CREB signal conduction.