A great body of experimental evidence indicates that the TAp63 isoforms can induce cell death through a canonical p53 responsive DNA binding site. In contrast, the Np63 proteins can act in a dominant nega tive manner toward p53 mediated transcriptional activa tion. Both TA and N transcripts can undergo alternative splicing, leading to the selleck catalog formation of three C terminal variants, denoted, B and, which further increase the diversity of the p63 proteins. Several interesting studies have clearly demonstrated that the Np63 isoform plays an important role Inhibitors,Modulators,Libraries in the main tenance of the conjunctival and corneal stem cells, while Np63B and Np63�� contribute to the regulation of cell differentiation and regeneration in the conjunctiva, lim bus and cornea.

Although Inhibitors,Modulators,Libraries the importance of p63 in the homeostasis of the ocular surface is widely accepted, the effects of infectious agents on the expres sion of this transcription factor family have not yet been investigated in epithelial cells of the eye. Herpetic keratitis is a vision threatening viral disease of the eye that is the major infectious cause of blindness in the developed countries. The causative agent, Herpes simplex virus 1 is a member of the Her pesviridae family comprising large, enveloped DNA viruses. Primary herpetic keratitis can develop directly via front door route infection by droplet spread, or via a back door route, which involves the indirect spread of HSV 1 to the cornea from a non ocular site. HSV 1 infection may affect all three corneal layers, leading to epithelial, stromal and endothelial keratitis, respectively.

Epithelial keratitis can be characterized by the appearance of branching dendritiform, or enlarged geographic ulcers. Stromal keratitis and endothelitis can result in stromal scarring, thinning, neovasculariza tion, Inhibitors,Modulators,Libraries severe iridocyclitis and an elevated intraocular pres sure. Most cases of corneal ulceration will eventually resolve, though recurrent Inhibitors,Modulators,Libraries infections impair the corneal function and lead to a vision impairment that may even necessitate penetrating keratoplasty. Previous studies have revealed that the mechanism of herpetic keratitis involves both immune and virus mediated cytopatho genic processes. Whereas the immune processes involved in the pathogenesis of herpetic ocular surface diseases have been investigated extensively, the molecular events implicated in the direct cytopathic Inhibitors,Modulators,Libraries action of HSV 1 remain largely unknown.

In the present study, we examined the effects of HSV 1 on the expression Dorsomorphin ALK of p63 and the Bcl 2 family member Bax in an effort to gain a better understanding of the ocu lar cytopathogenicity elicited by this virus. Methods Cell culture and HSV 1 growth The Staatens Seruminstitute Rabbit Cornea cell line, was grown in Dulbeccos modified Eagles minimal essential medium supplemented with 10% fetal calf serum at 37 C in a 5% CO2 atmo sphere.