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Relationship between matrix metalloproteinases MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinases-1 and IL-5, IL-8 in nasal polyps


Yue-Shih Chen MD
Department of Otorhinolaryngology
Plastic Head and Neck Surgery
University Hospital RWTH Aachen
Pauwelsstrasse 30
52057 Aachen


Background:  Nasal polyps (NP), a subgroup of chronic rhinosinusitis, are characterized by interleukin 5 (IL-5) mediated infiltration of eosinophils in sinus mucosa, leading to pseudostratified ciliated columnar epithelium, thickening of the epithelial basement membrane and tissue edema. Matrix metalloproteinases (MMP) constitute a large group of Zn2+ dependent endopeptidases with the ability to degrade extracellular matrix and are possibly responsible for the development of tissue edema in chronic sinusitis.

Objective:  The aim of this study was to determine the expression of MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) mRNA and to locate the distribution of MMP-2, MMP-9 and TIMP-1 by immunohistochemistry in ethmoid sinus mucosa in NP. Furthermore the correlation between IL-5 or IL-8 and MMP-2, MMP-9 or TIMP-1 is examined.

Methods:  Nasal polyps of 33 patients and 18 specimens of inferior turbinate mucosa were examined by real time RT-PCR for MMP-2, MMP-9, TIMP-1, IL-5 and IL-8 mRNA expression. Immunohistochemical labeling for MMP-2, MMP-9 and TIMP-1 was performed.

Results:  Differences between both locations were detectable for MMP-9 (P < 0.001) and IL-5 (P = 0.003) but not for MMP-2 (P = 0.278), TIMP-1 (P = 0.515) and IL-8 (P = 0.386). Correlation was detected only between TIMP-1 and IL-5 (r = 0.422, P = 0.014). Cytoplasmic staining of MMP-2 was present in the apical part of the ciliated cells, submucosal glands and in smooth muscle cells. Matrix metalloproteinase-9 was expressed in surface epithelium, in seromucous glands and in polymorphonuclear cells.

Conclusions:  Expression of MMP-9 and IL-5 mRNA are associated with NP. The correlation between IL-5 and TIMP-1 indicates the role of TIMP-1 in maintaining the homeostasis in NP.