Rhinovirus upregulates matrix metalloproteinase-2, matrix metalloproteinase-9, and vascular endothelial growth factor expression in nasal polyp fibroblasts.
OBJECTIVE
Upregulation of matrix metalloproteinase (MMP) and vascular endothelial growth factor (VEGF) has been suggested to have an important role in the pathogenesis of nasal polyps (NPs). The aim of this study was to investigate the effect of rhinovirus (RV) infection on the expression of MMPs, tissue inhibitor of metalloproteinase (TIMP)-1, and VEGF in NP fibroblasts.


METHODS
NP fibroblasts (5 x 10(5) cells/mL) obtained from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) were infected with RV serotype 16 (RV-16) for 4 hours. The RV-16 infection was confirmed by seminested reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization. After 48 hours, MMP-2, MMP-9, TIMP-1, and VEGF protein levels were measured from culture supernatants by enzyme-linked immunosorbent assay. The changes in the expression of MMP-2, MMP-9, TIMP-1, and VEGF mRNA were assayed by RT-PCR.


RESULTS
RV-16 infection significantly enhanced the gene and protein expressions of MMP-2, MMP-9, and VEGF in NP fibroblasts, whereas TIMP-1 expression was not significantly affected by RV-16. MMP-2, MMP-9, and VEGF protein expression increased by 2.39-, 2.99-, and 3.02-fold, respectively, in RV-infected NP fibroblasts compared to noninfected controls. RV-16 infection also significantly upregulated the expression of MMP-2, MMP-9, and VEGF mRNA by 1.27-, 1.70-, and 1.53-fold, respectively, compared to control levels.


CONCLUSIONS
These in vitro findings suggest that RV infection may contribute to the pathogenesis of NP formation in patients with CRSwNP.
Wang
Jong Hwan
JH
Department of Otolaryngology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, South Korea.
Kwon
Hyun Ja
HJ
Jang
Yong Ju
YJ
D000328:Adult; D017931:DNA Primers; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009298:Nasal Polyps / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012229:Rhinovirus; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
D017931:DNA Primers; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9