PURPOSE: This study analyzed the influence of substance P (SP) on growth factors related to wound healing in mice in the presence of infectious keratitis. METHODS: Naturally resistant mice were injected intraperitoneally with SP or phosphate-buffered saline and infected with Pseudomonas aeruginosa, and corneal messenger RNA (mRNA) levels of growth factors and apoptosis genes were tested. Enzyme-linked immunosorbent assay determined the protein levels, whereas immunohistochemistry tested the distribution, macrophage phenotype, and cell quantitation. In vitro, macrophages were stimulated with lipopolysaccharide (LPS; with or without SP) and mRNA levels of proinflammatory and antiinflammatory cytokines and apoptosis genes were tested. RESULTS: After SP, epidermal growth factor mRNA and protein levels were disparately regulated early, with no differences later in the disease. Hepatocyte growth factor and fibroblast growth factor-7 mRNA and protein levels were increased after SP treatment. Enumerating dual-labeled stromal cells revealed no difference between SP-treated versus phosphate-buffered saline-treated groups in the percentage of epidermal growth factor-labeled fibroblasts or macrophages, but there were significant increases in both hepatocyte growth factor- and fibroblast growth factor-7-labeled cells. Type 2 (M2) macrophages and caspase-3 mRNA levels were decreased, whereas B-cell lymphoma-2 mRNA expression was increased after SP treatment. In vitro, mRNA levels of several proinflammatory cytokines and B-cell lymphoma-2 were elevated, whereas transforming growth factor β was decreased after macrophage stimulation with SP (with LPS) over LPS alone. (Mice: n = 105 control; 105 experimental.) CONCLUSIONS: These data show that treatment with SP in infectious keratitis elevates growth factors but also adversely affects the disease by enhancing the inflammatory response and its sequelae.
PURPOSE: This study analyzed the influence of substance P (SP) on growth factors related to wound healing in mice in the presence of infectious keratitis. METHODS: Naturally resistant mice were injected intraperitoneally with SP or phosphate-buffered saline and infected with Pseudomonas aeruginosa, and corneal messenger RNA (mRNA) levels of growth factors and apoptosis genes were tested. Enzyme-linked immunosorbent assay determined the protein levels, whereas immunohistochemistry tested the distribution, macrophage phenotype, and cell quantitation. In vitro, macrophages were stimulated with lipopolysaccharide (LPS; with or without SP) and mRNA levels of proinflammatory and antiinflammatory cytokines and apoptosis genes were tested. RESULTS: After SP, epidermal growth factor mRNA and protein levels were disparately regulated early, with no differences later in the disease. Hepatocyte growth factor and fibroblast growth factor-7 mRNA and protein levels were increased after SP treatment. Enumerating dual-labeled stromal cells revealed no difference between SP-treated versus phosphate-buffered saline-treated groups in the percentage of epidermal growth factor-labeled fibroblasts or macrophages, but there were significant increases in both hepatocyte growth factor- and fibroblast growth factor-7-labeled cells. Type 2 (M2) macrophages and caspase-3 mRNA levels were decreased, whereas B-cell lymphoma-2 mRNA expression was increased after SP treatment. In vitro, mRNA levels of several proinflammatory cytokines and B-cell lymphoma-2 were elevated, whereas transforming growth factor β was decreased after macrophage stimulation with SP (with LPS) over LPS alone. (Mice: n = 105 control; 105 experimental.) CONCLUSIONS: These data show that treatment with SP in infectious keratitis elevates growth factors but also adversely affects the disease by enhancing the inflammatory response and its sequelae.
Authors: Xiaoyu Jiang; Sharon A McClellan; Ronald P Barrett; Elizabeth A Berger; Yunfan Zhang; Linda D Hazlett Journal: Invest Ophthalmol Vis Sci Date: 2011-08-03 Impact factor: 4.799
Authors: Zimei Zhou; Minhao Wu; Ronald P Barrett; Sharon A McClellan; Yunfan Zhang; Linda D Hazlett Journal: Invest Ophthalmol Vis Sci Date: 2009-12-17 Impact factor: 4.799
Authors: Xiaoyu Jiang; Sharon A McClellan; Ronald Barrett; Megan Foldenauer; Linda D Hazlett Journal: Invest Ophthalmol Vis Sci Date: 2014-04-09 Impact factor: 4.799
Authors: Juan Mo; Sudha Neelam; Jessamee Mellon; Joseph R Brown; Jerry Y Niederkorn Journal: Invest Ophthalmol Vis Sci Date: 2017-01-01 Impact factor: 4.799