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

Fang Bian, Changjun Wang, Johanna Tukler-Henriksson, Stephen C. Pflugfelder, Caterina Camodeca, Elisa Nuti, Armando Rossello, De Quan Li, Cintia S. de Paiva

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2506-2516
Number of pages11
JournalJournal of Cellular Physiology
Volume231
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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    Bian, F., Wang, C., Tukler-Henriksson, J., Pflugfelder, S. C., Camodeca, C., Nuti, E., Rossello, A., Li, D. Q., & de Paiva, C. S. (2016). MMP-8 Is Critical for Dexamethasone Therapy in Alkali-Burned Corneas Under Dry Eye Conditions. Journal of Cellular Physiology, 231(11), 2506-2516. https://doi.org/10.1002/jcp.25364