Tuberc Respir Dis TRD Tuberculosis and Respiratory Diseases 1738-3536 2005-6184 The Korean Academy of Tuberculosis and Respiratory Diseases 10.4046/trd.2006.61.3.256 Original Article Expression of Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 after Administration of Endotoxin in Diabetic Rats Seo Ki Hyun M.D. Choi Jae Sung M.D. Na Joo Ok M.D. Uh Soo Taek M.D. Kim Yong Hoon M.D. http://orcid.org/0000-0003-2977-0255 Park Choon Sik M.D. Department of Internal Medicine, Soonchunhyang University College of Medicine, Clinical Research institute, Cheonan, Korea. Address for correspondence: Yong Hoon Kim, M.D. Department of Internal Medicine, Soonchunhyang University Hospital, 23-20, BongMyung-Dong, Cheonan, 330-721, Korea. Phone: 041-570-2124, Fax: 041-574-5762, welkim@schch.co.kr 09 2006 30 09 2006 61 3 256 264 24 04 2006 04 09 2006 Copyright © 2006 The Korean Academy of Tuberculosis and Respiratory Diseases 2006 Background

An acute lung injury(ALI) is characterized by the recruitment, activation, and apoptosis of inflammatory cells, numerous products released by inflammatory cells such as reactive oxygen species, inflammatory mediators, and a variety of proteolytic enzymes. It was reported that bacterial infections in diabetics showed impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflamed tissue. However, the effect of the proteinase - inhibitor (MMP-9 vs TIMP-1) in ALI in diabetics is unclear. This study evaluated the differences in the expression of MMP-9 and TIMP-1 after the stimulation of endotoxin in a rat model.

 Methods

Six-week-old male Sprague-Dawley rats were classified into normal, DM, LPS and DM+LPS groups. The peripheral blood, BAL fluids, and lung tissues were obtained from individual rats. The MMP-9 activity was measured by gelatin zymography and the TIMP-1 level was measured by Western blotting.

 Results

The total BAL cells of the DM-LPS groups were significantly lower than the LPS groups (p < 0.01). The MMP-9 activities in the serum were higher in the DM+LPS groups than in the other groups. The MMP-9 activities in the BAL fluids were significantly higher in the DM+LPS group than in the normal and diabetic rats (p < 0.05). TIMP-1 expressions in the BAL fluids were significantly lower in the DM+LPS group than other groups (p < 0.05). The ratio between MMP-9 and TIMP-1 in the BAL fluids was significantly higher in the DM+LPS groups (p < 0.05).

 Conclusion

In ALI in diabetics the higher MMP-9 activity and lower TIMP-1 level are believed to prolonged and intensify the course of inflammation.

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MMP-9 hydrolytic activity in serum (upper) and BAL fluids (lower) by gelatin zymography (left) and comparison of MMP-9 activity in four groups (right) (N: normal, D: DM, L: LPS, DL: DM + LPS, M: MMP-9, 2 marker) (*p < 0.05 vs N and †p < 0.05 vs N, D)

TIMP-1 expression in serum (upper) and BAL fluids (lower) by western blot (left) and comparison of TIMP-1 expression in four groups (right) (N: normal, D: DM, L: LPS, DL: DM + LPS) (*p < 0.05 vs N, D, L)

MMP-9/TIMP-1 ratio in serum (upper) and BAL fluids (lower) (N: normal, D: DM, L: LPS, DL: DM + LPS) (*p: < 0.05 vs N, D, L and †p: < 0.05 vs N, D)

General characteristics of experimental rats.

*P < 0.01 compared with normal and DM groups

†P < 0.05 compared with normal and DM groups

‡P < 0.05 compared with normal, DM, and DM+LPS groups

§P < 0.05 compared with normal, DM, and LPS groups

∥LW: lung weight, BW: final body weight