title: Activation‑induced upregulation of MMP9 in mast cells is a positive feedback mediator for mast cell activation.
abstract: Activated mast cells are involved in the pathogenesis of allergic rhinitis (AR). As a member of the matrix metalloproteinase (MMP) family, MMP9 has been previously demonstrated act in a pro‑inflammatory manner. Mast cells regulate the activity of MMP9, and mast cells themselves have been reported to produce MMP9. However, to the best of our knowledge, the involvement of MMP9 in mast cell activation remains to be elucidated. The present study demonstrated an upregulation of MMP9 protein and mRNA expression levels in mast cells activated by phorbol ester and ionomycin. Phosphorylated ERK and AKT protein levels also markedly increased in activated mast cells, and inhibition of the ERK and AKT signaling pathways prevented the increase of MMP9 in activated mast cells. MMP9 was demonstrated to be involved in mast cell activation, since inhibition of MMP9 activity or expression inhibited mast cell activation. Furthermore, IL‑4 treatment reduced MMP9 upregulation in activated mast cells, and interference with IL‑4 signaling with an IL‑4 neutralizing antibody promoted MMP9 upregulation in activated mast cells. These results revealed a novel MMP9‑mediated mechanism underlying mast cell activation, thus providing novel ideas for AR therapy.
authors.affiliation: Department of Otolaryngology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D065631:Rhinitis, Allergic / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation
chemical_list: D012333:RNA, Messenger; D015847:Interleukin-4; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9