Matrix metalloproteinase (MMP)-9 is thought to be involved in the etiopathogenesis of chronic
rhinosinusitis (CRS) with
nasal polyps and cleaves
collagen IV, causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP-9 expression is negatively affected by
sirtuin (SIRT)-1 in human monocytotic cells,
retinal endothelial cells, and epithelial
carcinoma cells. However, it is unknown which factors affect MMP-9 expression and activity in human nasal epithelial cells (HNECs). To examine factors affecting MMP-9 expression and activity in HNECs, HNECs were stimulated with
Toll-like receptor (
TLR) agonists, followed by quantitative PCR, immunofluorescence, and zymography to examine MMP-9 expression and activity. MMP-9 expression was evaluated in sinonasal tissue of control subjects without CRS, and patients with CRS without
nasal polyps and those with CRS with
nasal polyps, in relation to the expression of
SIRT1 using a tissue microarray. The effect of
SIRT1 stimulation/inhibition on MMP-9 expression in HNECs was also tested. TLR3 agonists increased MMP-9
mRNA expression (473 fold, P = 0.0198) and activity (20.4-fold, P < 0.05).
SIRT1 activation or inhibition reciprocally affected MMP-9 expression in the presence of TLR3 agonists. MMP-9 and
SIRT1 expression within the epithelial layer of sinonasal tissue was inversely correlated only in patients with CRS but not in control subjects. TLR3 agonists increased MMP-9 expression and activity in HNECs, and the effect was abolished in the presence of
SIRT1 activation.
SIRT1 and MMP-9 expression was inversely correlated in CRS tissue, supporting
SIRT1 as a possible therapeutic target for
nasal polyp formation.