In vivo relationship between collagenase-2 and interleukin-8 but not tumour necrosis factor-alpha in chronic rhinosinusitis with nasal polyposis.
BACKGROUND
The characteristic feature of chronic rhinosinusitis with nasal polyposis (CRSwNP) is eosinophilic inflammation of the sinus mucosa; a type of inflammation also seen in asthmatic airways. Similar histopathologic findings of airway remodelling are present in both diseases. Remodelling is tightly controlled by matrix metalloproteinases (MMP). Increase of collagenase-2 (MMP-8) expression in the bronchial epithelial cells has been described in asthmatic patients, but it has not been studied in CRSwNP.


METHODS
The concentrations and degree of activation of MMP-8 were analysed by immunofluorometric assay and Western blotting, respectively, in sinus mucus samples from CRSwNP patients and in nasal lavages from healthy controls in relation to inductive cytokines interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha).


RESULTS
Significantly elevated levels of MMP-8 and IL-8 but not TNF-alpha were found in CRSwNP patients relative to controls. In particular, the activation of mesenchymal-type MMP-8 but not polymorphonuclear-type MMP-8 was associated with elevated IL-8 levels.


CONCLUSIONS
The IL-8 and MMP-8 seemingly form an inductive cytokine-proteinase cascade in CRSwNP pathogenesis. Together they provide a target for novel therapies and a diagnostic tool for monitoring CRSwNP treatment.
Kostamo
K
K
Department of Otorhinolaryngology, Helsinki University Central Hospital, Helsinki, Finland.
Sorsa
T
T
Leino
M
M
Tervahartiala
T
T
Alenius
H
H
Richardson
M
M
Toskala
E
E
D000368:Aged; D002908:Chronic Disease; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism; D009298:Nasal Polyps / Q000503:physiopathology*; D010256:Paranasal Sinuses / Q000378:metabolism; D012220:Rhinitis / Q000150:complications* / Q000503:physiopathology*; D012852:Sinusitis / Q000150:complications* / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D020784:Matrix Metalloproteinase 8