Effect of vascular cell adhesion molecule 1 on fibroblasts in human eosinophilic chronic rhinosinusitis.
The pathogenesis of eosinophilic chronic rhinosinusitis (ECRS) is still unclear. Paranasal mucosa inflammation is thought to be related to eosinophilic infiltration. This infiltration seems to induce changes in the expression of cell adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1). The E-cadherin-beta-catenin complex maintains the integrity of the epithelium. Downregulation of beta-catenin and E-cadherin is a pivotal factor for progressive cell growth. This study aimed to assess which cytokines regulate the expression of the adhesion molecule E-cadherin and the multi-functional protein beta-catenin, which plays a key role in cadherin-mediated anchoring in ECRS. Cultured ECRS specimens were incubated with human VCAM-1. After a period of up to 72 h, expression of E-cadherin and beta-catenin was determined using cytokine immunoassay and immunohistochemistry. In ECRS, significant increases in E-cadherin expression were found in fibroblast cell cultures. Stimulation with VCAM-1 did not produce a significant alteration in the expression of the adherens junction protein beta-catenin. In addition, VCAM-1 did not decrease the levels of membrane staining for adherens junction proteins. The selective increase in E-cadherin expression in eosinophilic fibroblast cultures might be explained by a higher concentration of the Th2-type cytokines in these cultures. The tissue remodelling observed during chronic eosinophilic inflammation offers new insight into the pathogenesis of ECRS.
Sauter
Alexander
A
Universitaets-HNO-Klinik, Theodor-Kutzer-Ufer, D-68135 Mannheim, Germany. alexander.sauter@googlemail.com
Bas-Orth
Daniel
D
Stern-Straeter
Jens
J
Barnes
James
J
Soulsby
Hannah
H
Hörmann
Karl
K
Naim
Ramin
R
D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D004802:Eosinophilia / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D012852:Sinusitis / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D019010:Vascular Cell Adhesion Molecule-1; D051176:beta Catenin