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E. A. Szliter, R. P. Barrett, Y. Zhang, L. D. Hazlett; VIP Down-Regulates Inflammatory Cell Infiltration in the Pseudomonas Aeruginosa Infected Cornea by Modulating ECM and Adhesion Molecule Expression. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5984.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies from our laboratory have provided evidence that vasoactive intestinal peptide (VIP) regulates cytokine/chemokine production and host inflammatory cell function to promote resistance against P. aeruginosa corneal infection in normally susceptible C57BL/6 (B6) mice (J. Immunol., in press 2006). This study tested the hypothesis that VIP also regulates extracellular matrix (ECM) and adhesion molecule expression, thus reducing cell migration/infiltration into the P. aeruginosa-infected cornea of susceptible B6 mice and promotes corneal healing and resistance.
B6 mice were injected i.p. with recombinant (r) VIP daily from -1 through 5 days p.i. Control mice were similarly injected with PBS. Real-time RT-PCR, ELISA and immunohistochemistry (IHC) were used to assess the effects of rVIP treatment in regulation of ECM and adhesion molecule expression.
Injection of B6 mice with rVIP vs. PBS resulted in disparate expression of adhesion molecules and ECM components as detected by real-time RT-PCR. mRNA analysis revealed that corneas of rVIP-treated mice had significantly increased levels for molecules such as: TGF-ß1, ITG-α1 and 2, MMP-9 and -14, and CD44 at 3 and 5 days p.i.; while others including: COL8A1, COL15A1, ICAM-1, VCAM-1, PECAM-1 MMP-2, -3, -7, and -12, ITG-αL, ITG-ß3, SEL-L and -P were significantly down-regulated when compared to PBS-treated animals. Protein levels for ICAM-1 and VCAM-1 supported mRNA data at similar time points, as detected by ELISA. Selective IHC confirmed the effects of rVIP treatment, showing reduced corneal expression of both ICAM-1 and LFA-1 at 1 day p.i. when compared to PBS-treated animals.
rVIP treatment down-regulates the production of adhesion molecules integral to the transmigration process of host inflammatory cells (PMN, macrophages) into the infected cornea. This results directly in reduced cellular infiltration, less stromal destruction and better disease outcome.
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