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Megan E. Foldenauer, Sharon A. McClellan, Yunfan Zhang, Linda D. Hazlett; Substance P vs. VIP Inhibition Disparately Affects Growth Factors In Pseudomonas aeruginosa-infected BALB/c Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5813.
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The pro-inflammatory neuropeptide Substance P (SP) has dual-affects: exacerbating infection (Pseudomonas aeruginosa keratitis), but also may promote non-infectious wound healing. Therefore, this study determined the affect of exogenous SP vs. inhibition of the anti-inflammatory neuropeptide, vasoactive intestinal peptide (VIP) on growth factor (GF) production in the cornea of resistant BALB/c mice where SP or VIP antagonist treatment exacerbates keratitis.
BALB/c mice received intraperitoneal injections of SP or VIP antagonist (sterile saline for controls) from the day before infection until 5 to 7 days post-infection (p.i.). Corneas were harvested at days 1-7 p.i. and tested for mRNA levels of epidermal growth factor (EGF), hepatocyte growth factor (HGF), and keratinocyte growth factor (KGF/FGF-7) using real-time RT-PCR. Similar experiments used ELISA and immunostaining (IHC) to determine GF protein levels, their corneal distribution and cellular origin.
After infection, the cornea of SP or VIP antagonist- vs. control-treated BALB/c mice show increased disease. In this regard, after SP treatment, EGF mRNA and protein levels were disparately regulated at 1 day p.i., but neither differed between groups later in disease. In contrast, both HGF and KGF mRNA and protein levels were increased after SP treatment. IHC data (5 days p.i.) revealed spatial distribution differences between the two groups in the corneal epithelium and stroma and in stromal fibroblasts. In contrast, after VIP antagonist vs. control treatment, EGF mRNA levels were down-regulated, while HGF and KGF mRNA levels were not significantly different between groups.
These data provide evidence that SP vs. VIP antagonist treatment disparately regulate GF production after infection, suggesting that overall, the dual effects of SP promote GF production, but also enhance pro-inflammatory events.
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