[Regulatory effects of inhaled steroids on expression of matrix metalloproteinase-9 and its inhibitor in asthmatic rats].
OBJECTIVE
To investigate the role of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor (TIMP-1) in the pathogenesis of bronchial asthma and assess the effect of steroid treatment on MMP-9 and TIMP-1 levels. Matrix metalloproteinases are a family of zinc and calcium-dependent endopeptidases. Many MMPs such as MMP-1, MMP-2, MMP-3 are associated with asthma, in which MMP-9 is the key factor in asthma. Tissue inhibitor-1 of metalloproteinases is a specific inhibitor of MMP-9; the MMP-9 and TIMP-1 imbalance could lead to airway inflammation and remodeling in lung disease such as asthma.


METHODS
Forty Wistar rats were divided into 4 groups randomly: control, asthma model 7 days (7-day group), asthma model 21 days (21-day group) and steroid treatment groups. Asthma model of rats were established by ovalbumin (OVA) sensitization and challenge with mist inhalation. The expression of MMP-9 and TIMP-1 in lung tissues was detected by immunocytochemistry, RT-PCR and Western blotting.


RESULTS
(1) By observing the changes of action, tracing respiratory curves, detecting level of serum IgE level and observing the lung tissues sections, the authors demonstrated that the rat asthmatic models were successfully established. (2) The lung tissue sections of the asthma groups stained with hematoxiline and eosin (HE) showed many inflammatory cell infiltrations around the bronchioli and accompanying arterioles, hyperplasia of caliciform cells, broken bronchial mucous membrane and thickening of submucosal layer. The hyperplasia of airway smooth muscle and basement membrane were more significant in asthma model 21-day group than that in 7-day group. These changes were improved after treatment. (3) The expression of MMP-9 in rat's lung tissues: the expression was 2.71 +/- 0.37 in 7-day group, 1.76 +/- 0.27 in 21-day group, 0.88 +/- 0.18 in the treatment group and 0.52 +/- 0.10 in the control group (F = 151.52, P < 0.01). The expression of TIMP-1 in rat's lung tissues was 1.13 +/- 0.19 in the 7-day group, 1.55 +/- 0.24 in 21-day group, 0.77 +/- 0.15 in the treatment group and 0.47 +/- 0.08 in the control group (F = 69.46, P < 0.01). (4) The results of immunocytochemistry and protein expression were consistent with those of RT-PCR.


CONCLUSIONS
The protein and mRNA expression level of MMP-9 and TIMP-1 was high in asthmatic rat's lung tissues. Down-regulation of the expression of MMP-9 and TIMP-1 by steroids may be one of the mechanisms by which airway inflammation and remodeling are inhibited in asthma.
Qiao
Hong-mei
HM
Department of Pediatrics, The First Hospital of Jilin University, Changchun 130021, China.
Lu
Ji-rong
JR
Cheng
Huan-ji
HJ
Liu
Li
L
Ma
Qing-shan
QS
Fu
Wen-yong
WY
Zhao
Fang-xing
FX
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
D005938:Glucocorticoids; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9