Effect of respiratory syncytial virus on the activity of matrix metalloproteinase in mice.
BACKGROUND
Respiratory syncytial virus (RSV) is a common pathogen in the lower respiratory tract of infants and children. Recent studies have shown that in adults, especially in the elderly population who have relatively weak immunity, lower respiratory tract infection is not uncommon. RSV was detected in 22% hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (COPD), and the detection rate was only next to that of parvovirus and influenza virus respectively. Further studies revealed that lung infection of RSV could lead to inflammatory destruction and structural remodeling. This study was undertaken to examine the effect of infection with RSV on matrix metalloproteinase (MMPs) in mice, and to explore the role of RSV in the pathogenesis of pulmonary diseases.


METHODS
Twenty BALB/c mice were divided randomly into an RSV infection group and a blank control group. The mice in the RSV infection group were given 100 microl liquid containing 10(6) PFU of RSV by intranasal instillation. Three days after the infection, the bronchoalveolar lavage fluid (BALF) was harvested and RT-PCR and Western blotting were used to detect MMP-9 and the expression of tissue inhibitors of matrix metalloproteinase (TIMP)-1 mRNA in lung tissues. Gelatin zymography was employed to detect the activities of MMP-9 and MMP-2 in BALF. Immunohistochemistry was used to determine the expressions of E-cadherin (E-cd) and proliferating cell nuclear antigen (PCNA) in the lung tissues.


RESULTS
In the BALF of the mice infected with RSV, the activities of MMP-9 and MMP-2 were significantly increased (t = 6.08, P < 0.01 and t = 5.68, P < 0.01). The levels of mRNA and proteins of MMP-9 in the lung tissues of the mice infected with RSV were significantly elevated, and the mRNA and protein levels were significantly higher than those of the blank controls. Though the ratio of MMP-9/TIMP-1 mRNA in the lung tissues of the infected mice was not significantly different from that of the normal controls, the ratio of the MMP-9/TIMP-1 protein in the RSV infection group was significantly higher than that in the control group. Moreover, the number of cells with positive E-cd expression was decreased and the number of cells positive for PCNA was increased, with an enhanced expression.


CONCLUSIONS
In mice, infection with RSV can significantly increase the activities of MMP-9 and MMP-2, and conspicuously elevate the mRNA transcription of MMP-9. RSV infection can increase the activity of gelatinase while up-regulating its inhibitory factors but increase its protein ratio of MMP-9/TIMP-1 in lung tissues, thereby facilitating fibrosis after structural destruction of the airway. The resultant status might be an important factor causing chronic reconstruction of the airway.
Li
Wen
W
Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University College of Medicine, Institute of Respiratory Diseases Zhejiang University, Hangzhou 310009, China.
Shen
Hua-Hao
HH
D000818:Animals; D015820:Cadherins / Q000032:analysis; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000821:virology; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D018357:Respiratory Syncytial Virus Infections / Q000201:enzymology*; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification
D015820:Cadherins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9