p38 mitogen-activated protein kinase modulates expression of tumor necrosis factor-related apoptosis-inducing ligand induced by interferon-gamma in fetal brain astrocytes.
This study describes the involvement of the p38 mitogen-activated protein kinase (MAPK) during interferon-gamma (IFN-gamma) signaling in fetal brain astrocytes. In some pathological conditions of brain, p38 MAPK transduces stress-related signals, increases expression of proinflammatory cytokines, and induces cellular damage or apoptosis. In astrocytes, the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) expression level was increased by IFN-gamma. AG490, a JAK inhibitor, blocked TRAIL expression induced by IFN-gamma. SB203580, a specific p38alpha and p38beta2 MAPK inhibitor, decreased the TRAIL expression induced by IFN-gamma. The phosphorylation of the Ser727 site of STAT1, but not the Tyr701 site, was inhibited by SB203580. These results suggest that p38 MAPK modulates STAT1 phosphorylation in IFN-gamma signaling in fetal brain astrocytes.
Lee
J
J
Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Shin
J-S
JS
Park
J Y
JY
Kwon
D
D
Choi
S-J
SJ
Kim
S-J
SJ
Choi
I-H
IH
D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000378:metabolism*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases
D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases