Expression of membrane-type matrix metalloproteinases 4, 5, and 6 in mouse corneas infected with P. aeruginosa.
OBJECTIVE
To investigate the expression and regulation of membrane-type matrix metalloproteinases (MT-MMPs) 4, 5, and 6 in the mouse corneas infected with Pseudomonas aeruginosa.


METHODS
C57BL/6J mice were intracorneally infected with P. aeruginosa. The expression of MT4-, MT5-, and MT6-MMP was detected at both the mRNA and protein levels by RT-PCR and immunoblot analysis. Immunohistochemical staining was performed to localize the expression of MT4- and MT5-MMP in the mouse corneas.


RESULTS
Expression of MT4- and MT5-MMP was detected in the normal (uninfected) cornea by RT-PCR and immunoblot analysis. When infected with P. aeruginosa, the corneas showed significant induction of each MT-MMP. Localization of MT4- and MT5-MMP revealed that the expression of MT5-MMP was restricted to the epithelial tissue in the normal cornea, whereas the induced expression of MT4- and MT5-MMP was predominantly in the substantia propria, which contained most of the infiltrating cells. MT6-MMP expression was not detected in the uninfected cornea but was upregulated in the infected corneas.


CONCLUSIONS
Expression of MT4-, MT5-, and MT6-MMP was induced in corneas infected with P. aeruginosa. Immunohistochemistry showed predominant immunoreactivity of MT4- and MT5-MMP in the substantia propria. Previous histologic studies have revealed different patterns of inflammatory cell infiltration with an increased number of polymorphonuclear neutrophils (PMNs) during the early stage of inflammation and increased macrophages during the late stage. These results indicate a good correlation between the overexpression of the MT-MMPs in the infected corneas and the inflammatory response-that is, leukocyte infiltration-indicating that inflammatory cells such as macrophages and PMNs may play a role in the upregulation of MT-MMPs during corneal infection, which in turn can cause the destruction of corneal tissue.
Dong
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Department of Immunology and Microbiology, Wayne State University School of Medicine, 540 E. Canfield, Detroit, MI 48201, USA.
Katar
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Alousi
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Berk
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D000818:Animals; D003315:Cornea / Q000201:enzymology*; D003316:Corneal Diseases / Q000201:enzymology*; D058851:GPI-Linked Proteins; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011552:Pseudomonas Infections / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D014018:Tissue Distribution
D058851:GPI-Linked Proteins; D012333:RNA, Messenger; C492243:MMP24 protein, human; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C498537:Mmp17 protein, mouse; C118502:Mmp24 protein, mouse; C403928:matrix metalloproteinase 25