The Nuclear-Factor kappa B Pathway Is Activated in Pterygium

PURPOSE. Pterygium is a prevalent ocular surface disease with unknown pathogenesis. The authors investigated the role of nuclear factor kappa B (NF-kappa B) transcription factors in pterygium. METHODS. Surgically excised primary pterygia were studied compared with uninvolved conjunctiva tissues. NF-kappa B activation was evaluated using Western blot analysis, ELISA, and DNA-binding assays. Primary pterygium fibroblasts were treated with TNF-alpha (20 ng/mL), and NF-kappa B activation was evaluated using immunocytochemistry, Western blot analysis, phospho-I kappa B alpha ELISA, and DNA-binding assays. TNF-alpha stimulation of NF-kappa B target genes RelB, NFKB2, RANTES, MCP-1, ENA-78, MMP-1, MMP-2, and MMP-3 in pterygium fibroblasts was compared with that in primary tenon fibroblasts by real-time PCR. RESULTS. Phosphorylation of I kappa B alpha (Ser32) was increased in pterygia tissues compared with uninvolved conjunctiva tissues, as determined by Western blot analysis and ELISA. I kappa B alpha expression was decreased, whereas nuclear RelA and p50 DNA-binding capacities were increased. Within 30 minutes of treatment with TNF-alpha, pterygium fibroblasts showed increased I kappa B alpha phosphorylation and nuclear translocation of RelA and p50. Treatment with TNF-alpha beyond 12 hours resulted in increased nuclear expression of RelB, p100, and p52. Furthermore, the upregulation of RANTES, MCP-1, ENA-78, MMP-1, MMP-2, and MMP-3 expression was more pronounced in TNF-alpha-treated pterygium fibroblasts than in tenon fibroblasts. CONCLUSIONS. The NF-kappa B pathway is shown for the first time to be activated in pterygia tissues compared with normal conjunctiva tissues. Stimulation by the inflammatory cytokine TNF-alpha can activate both canonical and noncanonical NF-kappa B pathways in pterygium fibroblasts with concomitant upregulation of NF-kappa B target genes. (Invest Ophthalmol Vis Sci. 2011; 52: 230-236) DOI: 10.1167/iovs.10-5735