The Expression And Role Of VIP In The Cornea Infected By Aspergillus Fumigatus

Objective: To determine the expression of VIP in susceptible C57BL/6 and resistant BALB/c during Aspergillus fumigatus(A.fumigatus)keratitis and to determine the role of vasoactive intestinal peptide(VIP)in A.fumigatus-infected corneas.Methods:(1)VIP expression was tested in normal and infected cornea of susceptible C57BL/6 and resistant BALB/c mice.The cornea was Infected with Aspergillus fumigatus hyphae,established model of mouse fungal keratitis.PCR was used to test the VIP m RNA expression in normal and infected corneas of 1?3and 5 days.(2)BALB/c mice were pretreated with VIP antagonist.The disease was monitored using a slit lamp microscope and scored for comparison of symptoms.Mice were infected and clinical score were recorded.At 3 days postinfection,the pro-inflammatory MIP-2?IL-1??TNF-?m RNA and the anti-inflammatory IL-10?TGF-? m RNA levels of normal and infected corneas were tested by PCR;MIP-2?IL-1??TNF-??IL-10?TGF-?protein levels were tested by ELISA at 3 and 5 days postinfection.Results:(1)Both mouse strains showed consitutive espression of corneal VIP.The VIP m RNA was elevated significantly in BALB/c miceover C57BL/6 mice at 1 and 3 days postinfection.And was no different at 5 days postinfection.The VIP m RNA expression were detected in normal cornea of either group.(2)With the VIP antagonist treatment of BALB/c mice showed increased disease significantly and decreased corneal opacity and resistance to corneal perforation compared with PBS controls.Treatment with VIP antagonist vs PBS treated BALB/c mice also demonstrated up-regulation of corneal m RNA and protein levels for pro-inflammatory cytokines:MIP-2 ? IL-1?and TNF-?,whereas anti-inflammatory mediators,IL-10 and TGF-?,were down-regulated.BALB/c mice treated with VIP antagonists increased the progress of keratitis and the clinical score also increased.Conclusion:(1)Data provide evidence that VIP expression is higher in BALB/c vs C57BL/6 cornea after infection.(2)VIP antagonist resulted in up-regulated inflammation of BALB/c mice,and increased the disease progression.(3)VIP can control the progress of inflammation by down-regulates pro-and up-regulates inflammatory mediators.