Regulation of Nerve Growth Factor mRNA by Interleukin-1 in Rat Hippocampal Astrocytes Is Mediated by NFκB

Abstract

Cytokines such as interleukin-1␤ (Il-1) are produced in the brain during development and during inflammatory processes that result from lesions or disease. One function of Il-1 in the brain appears to be the stimulation of astrocytes to proliferate and produce a variety of cytokines and trophic factors, including nerve growth factor. The mechanisms by which Il-1 exerts its actions on astrocytes remain poorly defined. We present evidence that this cytokine elicits activation of the NFB transcription factor and that this transcription factor mediates effects of Il-1 on nerve growth factor mRNA expression. Elucidation of the processes by which cytokines activate astrocytes and influence trophic factor expression may provide insight into mechanisms governing inflammatory processes within the central nervous system.

NFκB Activation Is Required for the Neuroprotective Effects of Pigment Epithelium-derived Factor (PEDF) on Cerebellar Granule Neurons

“…Mattson et al (18) report that increased expression of Mn-SOD contributes to the neuroprotective action of TNF-␣. Expression of neurotrophic factors such as NGF and GDNF is also regulated by NFB activation (46,53,54). In this study, transient induction of Bcl-2, Bcl-x, and Mn-SOD mRNA expression as well as NGF, BDNF, and GDNF mRNA was observed in PEDF-treated immature neurons (DIV2).…”

Cell Type-Specific Interleukin-1β Signaling in the CNS

“…We and others have shown previously that NF-B is activated by IL-1␤ in CNS astrocytes and mediates induction of growth factors and cytokines (Sparacio et al, 1992;Friedman et al, 1996). However, in contrast to astrocytes, no activation of NF-B was observed in cultured hippocampal neurons after exposure to IL-1 (Fig.…”

“…Nuclear extracts were prepared from control or IL-1␤-treated hippocampal neurons or astrocytes by a modification (Friedman et al, 1996) of the method of Dignam et al (1983). Nuclear protein (5 g) was incubated with 32 P-labeled oligonucleotides with the consensus sequences for either NF-B or cAMP response element (CRE).…”

“…The most well characterized pathway involves a kinase cascade leading to activation of the nuclear factor-B (NF-B) transcription factor (Croston et al, 1995;Cao et al, 1996;Malinin et al, 1997;Régnier et al, 1997). NF-B activation in glia mediates the regulation of cytokines and growth factors by IL-1 (Sparacio et al, 1992;Friedman et al, 1996;Heese et al, 1998). However, other signal-transducing pathways also can be activated by IL-1␤, including the p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathways (O'Neill, 2002;Dunne and O'Neill, 2003).…”

Effect of transgenic GDNF expression on gentamicin-induced cochlear and vestibular toxicity

“…19 In other tissues, an increase in the population of T cells or cytokines has been shown to upregulate the expression of neurotrophins, such as nerve growth factor (NGF), BDNF and NT-3, as well as GDNF. [30][31][32] The relationship between inflammatory reactions and production of growth factors has been demonstrated in a variety of systems and species as well as in cultured cells. 33,34 We speculate that the immune response due to Ad.LacZ might elevate the level of growth factors in the inner ear, leading to the protection of hair cells against aminoglycoside-induced ototoxicity.…”