Abstract
We investigated the effect of soluble IL-6R (sIL-6R) blockade on corneal inflammation. Topical instillation of either anti-IL-6R antibody (MR16-1) or phosphate buffered saline (PBS) was applied after wounding BALB/c mice corneas with alkali burn. The vascularized area was significantly reduced in the MR16-1 group. The immunoreactivity of phosphorylated STAT3, Gr-1, and F4/80 diminished significantly in the MR16-1 group. Laser capture microdissection resulted in a significant down-regulation of the mRNA expressions of ICAM-1, MCP-1, and VEGF-A in the corneal stroma of the MR16-1 group. Adding a combination of recombinant IL-6 and sIL-6R resulted in a significant increase in the release of VEGF from human corneal fibroblasts. As the infiltration of inflammatory cells, the expression of phosphorylated STAT3, and the expressions of inflammatory-related molecules in the experimental model of corneal inflammation were significantly inhibited by topical instillation of MR16-1, we deduce that IL-6 trans-signaling plays a significant role in ocular surface inflammation and that the blockade of IL-6R contributes to the reduction in corneal inflammation.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / pharmacology*
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Antibodies, Monoclonal / pharmacology*
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Antibodies, Neutralizing / pharmacology*
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Burns, Chemical / etiology
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Burns, Chemical / metabolism
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Burns, Chemical / prevention & control*
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Cells, Cultured
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Chemokine CCL2 / metabolism
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Corneal Keratocytes / drug effects
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Corneal Keratocytes / metabolism
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Corneal Neovascularization / metabolism
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Corneal Neovascularization / prevention & control*
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Disease Models, Animal
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Eye Burns / chemically induced*
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Immunoenzyme Techniques
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Intercellular Adhesion Molecule-1 / metabolism
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Interleukin-6 / immunology
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Keratitis / metabolism
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Keratitis / prevention & control
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Male
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Mice
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Mice, Inbred BALB C
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Phosphorylation
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Receptors, Interleukin-6 / immunology*
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Reverse Transcriptase Polymerase Chain Reaction
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STAT3 Transcription Factor / metabolism
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Sodium Hydroxide
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Anti-Inflammatory Agents
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Antibodies, Monoclonal
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Antibodies, Neutralizing
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Ccl2 protein, mouse
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Chemokine CCL2
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Icam1 protein, mouse
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Interleukin-6
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Receptors, Interleukin-6
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Vascular Endothelial Growth Factor A
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vascular endothelial growth factor A, mouse
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Intercellular Adhesion Molecule-1
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Sodium Hydroxide