Tuberc Respir Dis.  2006 Nov;61(5):447-455. 10.4046/trd.2006.61.5.447.

The Expression of MMPs and TIMPs in IPF and NSIP

• Kim YJ
• Kim JH
• Jeon HK
• Kim MK
• Jo YC
• Kyung SY
• An CH
• Lee SP
• Park JW
• Ha SY
• Jeong SH

• KMID: 1970250
• DOI: http://doi.org/10.4046/trd.2006.61.5.447

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. METHOD: 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.

Keyword

IIP; MMPs; TIMPs

MeSH Terms

Fibroblasts
Fibrosis
Gelatin
Gelatinases
Humans
Immunohistochemistry
Lung
Lung Neoplasms
Matrix Metalloproteinases*
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2
Gelatin
Gelatinases
Matrix Metalloproteinases
Tissue Inhibitor of Metalloproteinase-1
Tissue Inhibitor of Metalloproteinase-2

Figure

• 

  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).

• 

  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).

• 

  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.

• 

  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.

• 

  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.

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