Journal List > Tuberc Respir Dis > v.61(5) > 1001023

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Kim, Kim, Jeon, Kim, Jo, Kyung, An, Lee, Park, Ha, and Jeong: The Expression of MMPs and TIMPs in IPF and NSIP
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2006; 61(5): 447-455.

Published online: 30 November 2006

DOI: https://doi.org/10.4046/trd.2006.61.5.447

The Expression of MMPs and TIMPs in IPF and NSIP

Yu Jin Kim, M.D., Jung Ho Kim, M.D., Hyo Keun Jeon, M.D., Mi Kyeong Kim, M.D., Young Chan Jo, M.D., Sun Yong Kyung, M.D., Chang Hyeok An, M.D., Sang Pyo Lee, M.D., Jung Woong Park, M.D., Seung Yeon Ha, M.D.1, Sung Hwan Jeong, M.D.

Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center, Incheon, Korea.

1Department of Pathology, Gachon Medical School Gil Medical Center, Incheon, Korea.

Address for correspondence: Sung Hwan Jeong, M.D. Division of Pulmonary Medicine, Department of Internal Medicine, Gachon Medical School Gil Medical Center, Guwol-1-dong, Namdong-gu, Incheon, 405-760, Korea. Phone: 032-460-3818 Fax: 032-469-4320, jsw@gilhospital.com

Received 9 August 2006       Accepted 18 October 2006

Copyright © 2006 The Korean Academy of Tuberculosis and Respiratory Diseases

Abstract

Background

MMPs and TIMPs are important factors for abnormal remodeling the pulmonary parenchyme in idiopathic interstitial pneumonia(IIP) This study evaluated the expression of MMPs and TIMPs in the tissue of IPF, NSIP and normal control subjects.

Methods

The MMP-2 and -9 activity in the lung tissue was studied by gelatin zymography, and the expression of MMP-1, -2 ,-9, TIMP-1 and -2 in the lung tissue was measured by immunohistochemistry. Thirty five patients, who were diagnosed with IIP (UIP ; 22, NSIP ; 13), were enrolled in the immunohistochemical study. Thirteen patients with IIP (UIP ; 9, NSIP ; 4) and five patients with lung cancer were enrolled in the zymographic assay.

Results

(1) The immunohistochemistry for MMP-1,-2,-9, TIMP-1 and-2 ; MMP-1,-9 and TIMP-2 were stained stronger in the UIP subjects than NSIP and the normal control. TIMP-2 was strongly stained in the UIP tissue. particularly the fibroblasts in the fibroblastic foci. (2) Zymography for MMP-2 and MMP-9 revealed MMP-2 to have prominent expression in the UIP tissue than in the NSIP tissue.

Conclusions

These results suggest that the overexpression of the TIMPs and gelatinases in UIP might be important factors in the irreversible fibrosis of the lung parenchyme

Keywords: IIP, MMPs, TIMPs

Figures and Tables

Figure 1
Immunohistochemical detection of MMP-1 in lung tissue with UIP (A), MMP-1 with NSIP (B), TIMP-1 with UIP (C), TIMP-1 with NSIP (D), TIMP-2 with UIP (E), TIMP-2 with NSIP (F). Immunoreactive MMP-1(collagenase-1) for UIP (A) and MMP-1 for NSIP (B) is noticed in reactive alveolar and bronchiolar epithelial cells and in clusters of alveolar macrophages (× 400). Fibroblasts/myofibroblasts show a weak reaction for TIMP-1(C) (× 400). The TIMP-1 immunoreactivity of the epithelial cells lining the alveolar space are little. Macrophages show only a minimal increase in reactivity(D) (× 400). TIMP-2 is intensely stained in the interstitial cells located in subepithelial fibroblasts/myofibroblast foci(E) (× 400). Most areas of NSIP are negative for TIMP-2. Rare foci of myofibroblastic cells in NSIP show positive reaction of TIMP-2(F) (× 400).
trd-61-447-g001
Figure 2
Immunohistochemical detection of MMP-2 in lung tissue with UIP (A), MMP-2 with NSIP (B), MMP-9 with UIP(C), MMP-9 with NSIP(D). MMP-2 for UIP(A), MMP-2 for NSIP(B) is stained in the interstitial cells located in subepithelial fibroblast/myofibroblast foci (× 400). Fibroblast/myofibroblst in UIP show moderate reaction for MMP-9(C). Also MMP-9 for UIP(C), MMP-9 for NSIP(D) is moderate to stong stained in the neutrophils and lymphocytes (× 400).
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Figure 3
Gelatin zymograms of lung tissue from UIP, NSIP and normal controls. Gelatinolytic bands of 92 kD (proMMP-9), 85 kD (active MMP-9), 72 kD (proMMP-2), 66 kD (active MMP-2) are detected. Intense lytic bands corresponding to the MMP-9, and MMP-2 are visible in UIP. the bands of MMP-2 and -9 in NSIP and normal control were more less expressed than that UIP.
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Figure 4
Densitometric analysis of gelatinolytic bands for MMP-2 in lungs from UIP, NSIP, Normal control (NC).
*p<0.05
Densitometric analysis of gelatinolytic bands for active MMP-2 in lungs from UIP is higher than that of NSIP and NC. Also densitometric analysis of gelatinolyic bands for pro MMP-2 in lungs from UIP is higher than that of NSIP and NC.
trd-61-447-g004
Figure 5
Densitometric analysis of gelatinolytic bands for MMP-9 in lungs from UIP, NSIP, Normal control (NC).
*p<0.05
Densitometric analysis of gelatinolytic bands for active MMP-9 in lungs from UIP is higher than that of NSIP. Also densitometric analysis of gelatinolyic bands for pro MMP-9 in lungs from UIP is higher than that of NSIP.
trd-61-447-g005
Table 1
Immunoreactivity of components of lesions of IIP for MMP-1, -2, -9, TIMP-1 and 2.
trd-61-447-i001

The intensity of the immunohistochemical staining was graded as follows;

0, no reaction; 1, mild or weak staining; 2, moderate staining;

3, intense or strong staining; NSIP, nonspecific interstitial pneumonia;UIP, usual interstitial pneumonia.

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