title: Scutellarin attenuates human-neutrophil-elastase-induced mucus production by inhibiting the PKC-ERK signaling pathway in vitro and in vivo.
abstract: The aim of this study was to investigate the influence of scutellarin on mucus production induced by human neutrophil elastase (HNE) and the possible in vitro and in vivo mechanisms. To this purpose, cells were incubated with saline, scutellarin or gefitinib for 60 min and exposed to 0.1 μM HNE for 24 h. After being pretreated respectively with saline, scutellarin or gefitinib, rats were challenged intratracheally with HNE by means of nebulization for 30 days. The expression of mucin (MUC) 5AC, protein kinase C (PKC), and extracellular signal-regulated kinase 1/2 (ERK1/2) was assessed by ELISA, RT-PCR or Western blotting. The results showed that scutellarin inhibited MUC5AC mRNA and protein expressions induced by HNE in a concentration-dependent manner in vitro. In the in vivo model, scutellarin significantly attenuated MUC5AC mRNA expression and goblet cell hyperplasia in rats treated with HNE for 30 days, as well as decreased the phosporylation of PKC and ERK1/2 compared to the HNE control group. Therefore, our study showed that scutellarin could prevent mucus hypersecretion by inhibiting the PKC-ERK signaling pathway. Inhalation scutellarin may be valuable in the treatment of chronic inflammatory lung disease.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, China.
authors.forename: De-Peng
authors.initials: DP
authors.lastname: Jiang
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Juliy M
authors.initials: JM
authors.lastname: Perelman
authors.forename: Victor P
authors.initials: VP
authors.lastname: Kolosov
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Zhou
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D002460:Cell Line; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D049919:Erigeron; D005965:Glucuronates / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D055271:Mucin 5AC / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004365:Drugs, Chinese Herbal; D005965:Glucuronates; D055271:Mucin 5AC; C484876:scutellarin; D047310:Apigenin; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019272:Leukocyte Elastase