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Cornea:
doi: 10.1097/ICO.0b013e31824d6ffd
Basic Investigation

Substance P Affects Growth Factors in Pseudomonas aeruginosa–Infected Mouse Cornea

Foldenauer, Megan E. B. MA; McClellan, Sharon A. BS; Barrett, Ronald P. BS; Zhang, Yunfan MD; Hazlett, Linda D. PhD

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Abstract

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.

© 2012 Lippincott Williams & Wilkins, Inc.

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