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De Quan Li, Tie Yan Shang, Hyun-Seung Kim, Abraham Solomon, Balakrishna L. Lokeshwar, Stephen C. Pflugfelder; Regulated Expression of Collagenases MMP-1, -8, and -13 and Stromelysins MMP-3, -10, and -11 by Human Corneal Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2003;44(7):2928-2936. doi: 10.1167/iovs.02-0874.
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purpose. This study investigated the regulated expression of collagenases (MMP-1, -8, and -13) and stromelysins (MMP-3, -10, and -11) by human corneal epithelial cells treated with IL-1β, TNF-α, and doxycycline, a medication used to treat ocular surface diseases.
methods. Primary human corneal epithelial cell cultures were treated with IL-1β or TNF-α, with or without their corresponding inhibitors. Total RNA extracted from cells treated for 4 to 24 hours was subjected to semiquantitative RT-PCR and Northern hybridization. Conditioned media from 24-hour–treated cultures were evaluated for MMP production by ELISA and activity assays.
results. Semiquantitative RT-PCR and Northern hybridization revealed that the mRNAs of MMP-1, -13, -3, -10, and -11 were dose dependently upregulated by IL-1β and TNF-α, whereas MMP-8 and -14 and tissue inhibitor of metalloproteinase (TIMP)-1 were not altered, in corneal epithelial cells. MMP ELISA and activity assays confirmed this dose-dependent increase in MMP-1, -13, -3, and -10 protein production in conditioned media by IL-1β and TNF-α. This stimulated production was inhibited by their neutralizing antibodies and by IL-1 receptor antagonist. Doxycycline suppressed stimulated MMP-1, -10, and -13 production at both the mRNA and protein levels.
conclusions. This study demonstrated that IL-1β and TNF-α upregulate collagenases (MMP-1, -13) and stromelysins (MMP-3, -10, and -11) in human corneal epithelial cells. Doxycycline suppresses stimulated MMP-1, -13, and -10 at the mRNA and protein levels, which suggests that collagenases and stromelysins may play a role in the pathogenesis of sterile corneal ulceration and other ocular surface diseases.
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