TY - JOUR
T1 - IFN-γ inhibits AP-1 binding activity in human brain-derived cells through a nitric oxide dependent mechanism
AU - Conant, Katherine
AU - Ahmed, Umbereen
AU - Schwartz, Joan P.
AU - Major, Eugene O.
PY - 1998/8/1
Y1 - 1998/8/1
N2 - It has been demonstrated that CNS levels of the cytokine IFN-γ are elevated in association with a number of neuro-inflammatory diseases. In the present study, we have examined the effect of this cytokine on human brain derived cells. We show that prolonged treatment (22 h) of such cells with IFN-γ inhibits the DNA binding activity of transcription factor AP-1. Furthermore, we show that this effect can be reversed by either N(G)- monomethyl-L-arginine (L-NMMA) or L-N5-(1-iminoethyl)ornithine (L-NIO), competitive inhibitors of nitric oxide synthase activity [Rees et al., 1990]. In addition, we show that treatment of brain-derived cells with the nitric oxide donor 3-morpholinosydnonimine, HCl (SIN-1), or [N-(b-D-glucopyranosyl)- N2-acetyl-S-nitroso-D,L-penicillaminamide] (glyco-SNAP-1), also inhibits the binding activity of AP-1. Together, these results suggest that IFN-γ can inhibit AP-1 binding activity through a nitric oxide dependent mechanism.
AB - It has been demonstrated that CNS levels of the cytokine IFN-γ are elevated in association with a number of neuro-inflammatory diseases. In the present study, we have examined the effect of this cytokine on human brain derived cells. We show that prolonged treatment (22 h) of such cells with IFN-γ inhibits the DNA binding activity of transcription factor AP-1. Furthermore, we show that this effect can be reversed by either N(G)- monomethyl-L-arginine (L-NMMA) or L-N5-(1-iminoethyl)ornithine (L-NIO), competitive inhibitors of nitric oxide synthase activity [Rees et al., 1990]. In addition, we show that treatment of brain-derived cells with the nitric oxide donor 3-morpholinosydnonimine, HCl (SIN-1), or [N-(b-D-glucopyranosyl)- N2-acetyl-S-nitroso-D,L-penicillaminamide] (glyco-SNAP-1), also inhibits the binding activity of AP-1. Together, these results suggest that IFN-γ can inhibit AP-1 binding activity through a nitric oxide dependent mechanism.
KW - Astrocytes
KW - Interferon-γ
KW - Neurons
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Transcription factor AP-1
UR - http://www.scopus.com/inward/record.url?scp=0032146436&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032146436&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(98)00069-1
DO - 10.1016/S0165-5728(98)00069-1
M3 - Article
C2 - 9688322
AN - SCOPUS:0032146436
SN - 0165-5728
VL - 88
SP - 39
EP - 44
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -