| First Author | Ebihara N | Year | 2011 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 52 |
| Issue | 12 | Pages | 8549-57 |
| PubMed ID | 21989726 | Mgi Jnum | J:189455 |
| Mgi Id | MGI:5445834 | Doi | 10.1167/iovs.11-7956 |
| Citation | Ebihara N, et al. (2011) Role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing. Invest Ophthalmol Vis Sci 52(12):8549-57 |
| abstractText | PURPOSE: To investigate the role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing. METHODS: To assess the production of inflammatory molecules by corneal fibroblasts treated with supernatant derived from necrotic corneal epithelial cells, the authors used an antibody array. Expressions of membrane IL-6 receptor (mIL-6R) and soluble IL-6R (SIL-6R) by fibroblasts and epithelial cells were detected with flow cytometry and RT-PCR. Expressions of signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), and monocyte chemotactic protein-1 (MCP-1) by fibroblasts stimulated with IL-6 alone or IL-6/SIL-6R were determined by ELISA. The effect of IL-6 or IL-6/SIL-6R on epithelial cell migration was investigated in vitro by the scratch assay, whereas expressions of IL-6R and S100 A4 in the corneas of mice were detected by immunohistochemistry after incision of the corneal stroma. RESULTS: IL-1 derived from necrotic corneal epithelial cells induced the production of IL-6 by corneal fibroblasts. mIL-6R and SIL-6R mRNAs were expressed by both types of cells, although IL-6R protein at the cell surface was expressed only by epithelial cells. Expression of gp130 was detected in both types of cells. Activation of the IL-6 trans-signaling pathway induced the phosphorylation of STAT3, resulting in an increase of VEGF and MCP-1 production by corneal fibroblasts. Activation of the IL-6 classic-signaling pathway promoted the migration of corneal epithelial cells. IL-6R expression was also detected in activated fibroblasts and basal cells of the epithelium during the processes of wound healing in vivo. CONCLUSIONS: The IL-6 classic- and trans-signaling pathways have an important role in corneal sterile inflammation and wound healing. |
