The role of nerve growth factor in hyperosmolar stress induced apoptosis

Nerve growth factor (NGF) is a neurotrophic factor that plays an important role in the differentiation and growth of neuronal cells. It is also regarded as an inflammatory mediator in non‐neuronal tissues under physiological stress conditions. The mechanisms of NGF production and its roles in hyperosmolar stress conditions have not been established. In this study, we show that NGF levels in cultured human corneal epithelial cells (HCECs) were up‐regulated during hyperosmolar stress by IL‐1β, but not TNF‐α. NF‐κB activity, but not AP‐1, increased significantly under hyperosmolar conditions, and NF‐κB was involved in IL‐1β‐induced NGF production. IL‐1β‐induced NGF production reduced JNK phosphorylation and HCEC apoptosis. These changes were accompanied by down‐regulated Bax and caspase‐3, ‐8, ‐9 activities. NGF siRNA and the tyrosine kinase inhibitor K252a significantly enhanced Bax up‐regulation. Thus, up‐regulated NGF under hyperosmolar stress conditions may contribute, at least in part, to reduced HCEC apoptosis. This conclusion suggests that enhanced NGF expression may be beneficial in recovering corneal damage due to chronic hyperosmolar stress. J. Cell. Physiol. 216: 69–77, 2008. © 2008 Wiley‐Liss, Inc.