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

Wilma J Friedman,Sanjay Thakur,Lisa Seidman,Arnold B Rabson

doi:10.1074/jbc.271.49.31115

Abstract

Cytokines such as interleukin-1beta (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 NFkappaB 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.

Highlights

Astrocytes in the adult brain are normally quiescent; proliferation and activation of these cells occur in response to a number of stimuli, such as cytokines, associated with inflammation and disease
In contrast to the AP-1 pathway, recent studies have provided evidence for an Il-1 signaling pathway similar to that described for TNF␣, involving sphingomyelin metabolism and stimulation of a ceramide-dependent kinase leading to activation of the NF␬B transcription factor [19]
To determine the possible role of this pathway in mediating Il-1 actions in astrocytes, we initially examined whether providing the cells with ceramide would induce an increase in nerve growth factor (NGF) mRNA as effectively as Il-1

Summary

Introduction

Astrocytes in the adult brain are normally quiescent; proliferation and activation of these cells occur in response to a number of stimuli, such as cytokines, associated with inflammation and disease. Cytokine activation of astrocytes induces elevated levels of nerve growth factor (NGF) expression [6, 7, 8]. Cytokine stimulation of gene expression in a variety of cell types is mediated, at least in part, through activation of NF␬B transcription factors [21].

Results

Conclusion