TNF-α Decreases VEGF Secretion in Highly Polarized RPE Cells but Increases It in Non-Polarized RPE Cells Related to Crosstalk between JNK and NF-κB Pathways

• DOI: 10.1371/journal.pone.0069994
• Publication Date: 2013-07-29T17:33:06Z
• Authors: Hiroto Terasaki; Satoru Kase; Makoto Shirasawa; Hiroki Otsuka; Toshio Hisatomi; Shozo Sonoda; Susumu Ishida; Tatsuro Ishibashi; Taiji Sakamoto
• Keywords: Crosstalk

Asymmetrical secretion of vascular endothelial growth factor (VEGF) by retinal pigment epithelial (RPE) cells in situ is critical for maintaining the homeostasis retina and choroid. VEGF also involved development progression age-related macular degeneration (AMD). We studied effect tumor necrosis factor-α (TNF-α) on polarized non-polarized RPE (P-RPE N-RPE cells, respectively) culture rats. A subretinal injection TNF-α caused a decrease expression choroidal atrophy. Porcine were seeded Transwell™ filters, their maturation polarization confirmed asymmetrical trans electrical resistance. Exposure to decreased P-RPE but increased it culture. inactivated JNK activated NF-κB not cells. Inhibition both types indicating crosstalk between NF-κB. induced inhibitory effects because continuously inactivated. In however, was evident already activated. The basic activation pattern led opposing responses TNF-α. These results suggest that under inflammatory conditions depends cellular polarization, TNF-α-induced down-regulation may result atrophy physiological up-regulation cause neovascularization or non-physiological