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E. A. Szliter, R. P. Barrett, L. D. Hazlett; Vasoactive Intestinal Peptide Modulates Toll-Like Receptors and Related Signaling Molecules, Promoting Resistance After Pseudomonas Aeruginosa-Induced Corneal Infection. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2477. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Studies from our laboratory have demonstrated that vasoactive intestinal peptide (VIP) directly converts the normally susceptible C57/BL/6 (B6) mouse to resistant after P. aeruginosa induced keratitis. Previously we have shown that VIP regulates cytokine/chemokine production, host inflammatory cell function and extracellular matrix and adhesion molecules expression. This study tested the hypothesis that VIP also regulates Toll-like receptors (TLRs) and TLR-related molecules, modulating the inflammatory response and promoting corneal healing and resistance.
B6 mice were injected i.p. with recombinant (r) VIP daily from -1 through 7 days p.i. Control mice were similarly injected with PBS. In vitro stimulation assays also were performed using A6(1) cells to test the effects of VIP on corneal epithelial cells specifically. Real-time RT-PCR was used to assess rVIP treatment in the regulation of TLR and TLR-related molecule expression both in vivo and in vitro.
Injection of B6 mice with rVIP vs PBS resulted in disparate mRNA expression of TLR-4 and -9 transcript levels, as well as TLR-related molecules, including: MD-2, MyD88, CD14, SIGIRR, ST2 and IΚB. VIP treatment of corneal epithelial cells in vitro also resulted in differential expression of TLR4. However, in regards to TLR-related molecules, VIP enhanced expression of "anti-inflammatory" molecules; yet displayed no effect on "pro-inflammatory" TLR-related molecules at the mRNA level.
Treatment with rVIP down-regulates mRNA expression of TLR-4 and -9, in addition to "pro-inflammatory" TLR-related molecules such as MD-2, MyD88 and CD14. In contrast, corneal expression of "anti-inflammatory" TLR-related molecules (SIGIRR, ST2, IΚB) were enhanced after P. aeruginosa-induced ocular infection. The data from this study suggest a potential role for VIP in the regulation of disease pathogenesis via modulation of TLR functional pathways.
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