Poly(I:C)-Induced Adhesion Molecule Expression Mediated By Nf-Kappa B And Phosphoinositide 3-Kinase-Akt Signaling Pathways In Human Corneal Fibroblasts

PURPOSE. Viral infection at the ocular surface can lead to the chronic condition of viral stromal keratitis. Polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, induces the expression of adhesion molecules in cultured corneal fibroblasts. The authors investigated the roles of nuclear factor (NF)-kappa B and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways in the poly(I:C)-induced expression of adhesion molecules in corneal fibroblasts.METHODS. Human corneal fibroblasts were cultured with poly(I:C) in the absence or presence of I kappa B kinase 2 (IKK2) inhibitor (an inhibitor of NF-kappa B activation) or the PI3K inhibitor LY294002. The expression of vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, ICAM-2, and E-selectin, as well as the phosphorylation of the NF-kappa B inhibitory protein I kappa B-alpha and Akt, were examined by immunoblot analysis. The subcellular localization of adhesion molecules was determined by immunofluorescence analysis.RESULTS. Poly(I:C) increased the expression of VCAM-1 and ICAM-1 but not that of ICAM-2 or E-selectin in corneal fibroblasts. Poly(I: C) also induced the phosphorylation of I kappa B-alpha and Akt. The poly(I:C)-induced expression of VCAM-1 and ICAM-1 was attenuated by both IKK2 inhibitor and LY294002.CONCLUSIONS. The NF-kappa B and PI3K-Akt signaling pathways mediate the poly(I:C)-induced upregulation of VCAM-1 and ICAM-1 in corneal fibroblasts, with PI3K acting upstream of NF-kappa B activation. These pathways thus likely modulate local immune and inflammatory responses to viral infection in the corneal stroma. (Invest Ophthalmol Vis Sci. 2010;51:5556-5560) DOI: 10.1167/iovs.09-4909