Sirtuin-1 Controls Poly (I:C)-Dependent Matrix Metalloproteinase 9 Activation in Primary Human Nasal Epithelial Cells

• Published in: American journal of respiratory cell and molecular biology Vol. 59; no. 4; pp. 500 - 510
• Main Authors: Suzuki, Masanobu, Ramezanpour, Mahnaz, Cooksley, Clare, Li, Jian, Nakamaru, Yuji, Homma, Akihiro, Psaltis, Alkis, Wormald, Peter-John, Vreugde, Sarah
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01-10-2018
• Subjects: Cell culture; Chronic obstructive pulmonary disease; Collagen; Collagen (type IV); Diabetic retinopathy; Disease; Edema; Endothelial cells; Enzyme Activation - drug effects; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Gelatinase B; Gene expression; Gene Expression Regulation, Enzymologic - drug effects; Humans; Immune system; Immunofluorescence; Inflammatory diseases; Kinases; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Metalloproteinase; Molecular weight; Mucosa; Nose - pathology; Poly (I:C); Poly I-C - pharmacology; Polyps; Proteins; Retina; Rhinosinusitis; RNA, Messenger - genetics; RNA, Messenger - metabolism; SIRT1 protein; Sirtuin 1 - metabolism; Therapeutic applications; Time Factors; TLR3 protein; Toll-Like Receptor 3 - metabolism; Toll-like receptors; chronic rhinosinusitis; nasal polyps; Poly (I:C); MMP-9; SIRT1
• ISSN: 1044-1549; 1535-4989
• DOI: 10.1165/rcmb.2017-0415oc

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.