title: The MEK1/2-ERK1/2 pathway is activated in chronic rhinosinusitis with nasal polyps.
abstract: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease that has a considerable impact on the quality of life. Alterations in signalling pathways may contribute to the ongoing inflammation and proliferation in CRSwNP. The MEK1/2-ERK1/2 pathway transmits signals from many extracellular molecules to regulate cellular processes. We examined tissue samples from nasal polyps and the inferior turbinate of patients with CRSwNP and the inferior turbinate from subjects with healthy mucosa. The expressions of MEK1/2, ERK1/2, and their active phosphorylated forms pMEK1/2 and pERK1/2 were analysed using DNA microarray, quantitative real-time PCR, protein array, Western hybridisation, and immunohistochemistry. We detected increased MEK1/2 protein expression in nasal polyps compared to the inferior turbinates of patients with CRSwNP or healthy mucosa. We also found a higher amount of MEK1/2 in the inferior turbinates of patients with CRSwNP compared to those with healthy mucosa. Most importantly, we observed a significant increase in the phosphorylation of MEK1/2 and ERK1/2 in nasal polyps compared to both types of controls. We observed activation of the MEK1/2-ERK1/2 pathway in nasal polyps. Interestingly, we did not see the same activation pattern in different tiers of the MEK1/2-ERK1/2 signalling cascade. One explanation for this result is that the components enhance the complex MEK-ERK cascade in a distinct manner, enabling a wide variety of functions. The MEK1/2-ERK1/2 pathway appears to play a pivotal role in the pathogenesis of CRSwNP.
authors.affiliation: Department of Otorhinolaryngology and Facial Plastic Surgery, UK-SH, HNO-Klinik, University of Luebeck, Ratzeburger Allee 160, 23538, Luebeck, Germany, robert-linke@t-online.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Linke
authors.forename: Ralph
authors.initials: R
authors.lastname: Pries
authors.forename: Michael
authors.initials: M
authors.lastname: Könnecke
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Bruchhage
authors.forename: Robert
authors.initials: R
authors.lastname: Böscke
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gebhard
authors.forename: Barbara
authors.initials: B
authors.lastname: Wollenberg
mesh_terms: D002908:Chronic Disease; D006801:Humans; D020935:MAP Kinase Signaling System / Q000276:immunology; D046228:Microarray Analysis; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000378:metabolism*; D010766:Phosphorylation; D011788:Quality of Life; D012220:Rhinitis / Q000378:metabolism*; D012852:Sinusitis / Q000378:metabolism*