MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions.

Abstract

Our previous studies have shown that Dexamethasone (Dex) reduced the expression of matrix-metalloproteinases (MMPs -1,-3,-9,-13), IL-1β and IL-6, while it significantly increased MMP-8 mRNA transcripts in a concomitant dry eye and corneal alkali burn murine model (CM). To investigate if MMP-8 induction is responsible for some of the protective effects of Dex in CM, MMP-8 knock out mice (MMP-8KO) were subjected to the CM for 2 or 5 days and topically treated either with 2 μl of 0.1% Dexamethasone (Dex), or saline QID. A separate group of C57BL/6 mice were topically treated with Dex or BSS and received either 100 nM CAM12 (MMP-8 inhibitor) or vehicle IP, QD. Here we demonstrate that topical Dex treated MMP-8KO mice subjected to CM showed reduced corneal clarity, increased expression of inflammatory mediators (IL-6, CXCL1, and MMP-1 mRNA) and increased neutrophil infiltration at 2D and 5D compared to Dex treated WT mice. C57BL/6 mice topically treated with Dex and CAM12 IP recapitulated findings seen with MMP-8KO mice. These results suggest that some of the anti-inflammatory effects of Dex are mediated through increased MMP-8 expression. J. Cell. Physiol. 231: 2506-2516, 2016. © 2016 Wiley Periodicals, Inc.

• Authors: Fang Bian, Changjun Wang, Johanna Tukler-Henriksson, Stephen C Pflugfelder, Caterina Camodeca, Elisa Nuti, Armando Rossello, De-Quan Li, Cintia S de Paiva
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 231 Issue 11 Pg. 2506-16 (11 2016) ISSN: 1097-4652 [Electronic] United States
• PMID: 26923552 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2016 Wiley Periodicals, Inc.

Chemical References

• Alkalies
• Anti-Inflammatory Agents
• Matrix Metalloproteinase Inhibitors
• RNA, Messenger
• Dexamethasone
• Matrix Metalloproteinase 8

Topics

• Alkalies
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Burns, Chemical (complications, drug therapy, enzymology)
• Cornea (enzymology, pathology)
• Desiccation
• Dexamethasone (pharmacology, therapeutic use)
• Disease Models, Animal
• Dry Eye Syndromes (complications, enzymology)
• Eye Burns (complications, drug therapy, enzymology)
• Female
• Matrix Metalloproteinase 8 (deficiency, genetics, metabolism)
• Matrix Metalloproteinase Inhibitors (pharmacology, therapeutic use)
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophil Infiltration (drug effects)
• Neutrophils (drug effects, metabolism)
• RNA, Messenger (genetics, metabolism)
• Stress, Physiological