The role of nerve growth factor in hyperosmolar stress induced apoptosis

Abstract

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-1beta, but not TNF-alpha. NF-kappaB activity, but not AP-1, increased significantly under hyperosmolar conditions, and NF-kappaB was involved in IL-1beta-induced NGF production. IL-1beta-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.

Ciliary Neurotrophic Factor Promotes the Activation of Corneal Epithelial Stem/Progenitor Cells and Accelerates Corneal Epithelial Wound Healing

“…As one of the most innervated tissue, corneal nerve fibers maintain the homeostasis of corneal epithelium and exert a critical role in the normal corneal wound healing by secreting many trophic factors . Previous studies have reported the roles of neuropeptides and neurotrophic factors in the regulation of corneal epithelium and corneal wound healing, including the survival, proliferation, and stratification of corneal epithelial cells, expansion of corneal epithelial progenitor cells, and corneal nerve regeneration . However, the critical neurotrophic factor that maintains the homeostatic characteristics of corneal epithelium was not completely demonstrated.…”

Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain

“…IL-1β-mediated NGF expression involves nuclear factor kappa B (NF-κB) activity [50]. Interestingly, the proinflammatory effect of visfatin/NAMPT requires NF-κB activity in a NAMPT enzymatic activity-dependent manner.…”

The corneal epithelium: clinical relevance of cytokine-mediated responses to maintenance of corneal health

“…NGF is a mitogen and stimulates differentiation in vitro, but less so than does EGF (81)(82)(83)(84) . Furthermore, exogenous NGF has been shown to protect human corneal epithelial cells from hypertonicity-induced apoptosis in vitro (85) . During such a challenge, there is interleukin (IL)-1β up-regulation, which induces increases in NGF expression.…”

“…Clinically, situations that compromise the physical integrity of the cornea potentially lead to infection and development of opacities. One cytokine that is protective against cell loss through apoptosis is neural growth factor (NGF) (40) , while pro-inflammatory cytokines, i.e., tumor necrosis factor (TNF)α, act to promote apoptosis (41) . On the other hand, in vitro TNFα supports human corneal epithelial cell survival (42) .…”