Aspirin-induced blockade of NF-kappaB activity restrains up-regulation of glial fibrillary acidic protein in human astroglial cells.
The marked induction of glial fibrillary acidic protein (GFAP) has been observed in astrocytes during neuropathological processes accompanying reactive gliosis; however, the precise molecular mechanism(s) underlying this GFAP induction remains poorly resolved. Therefore, in this study, we examined whether the change of nuclear factor-kappa B (NF-kappaB) activity can influence GFAP expression levels. Aspirin, widely used to prevent NF-kappaB activity, reduced the levels of GFAP mRNA and protein in human astroglial cells including human glioblastoma A172 cells and primary human brain astrocyte cells (HBAs). Furthermore, aspirin inhibited the effects of hypoxic injury on the up-regulation of GFAP expression in HBAs. We confirmed the repressive effect of aspirin on GFAP transcription by GFAP promoter-driven reporter assay and found that one NF-kappaB binding site conserved in the mouse and human GFAP gene promoters is critical for this effect. To further delineate whether NF-kappaB is directly involved in the regulation of GFAP gene expression, we transfected A172 cells with an expression vector encoding a super-repressor IkappaBalpha protein (IkappaBalpha-SR) to specifically inhibit NF-kappaB activity and found the marked reduction of GFAP protein levels in IkappaBalpha-SR-transfectant cells. Taken together, our results suggest that NF-kappaB may play pivotal roles in GFAP gene expression.
Bae
Moon-Kyoung
MK
Department of Oral Physiology, College of Dentistry, Pusan National University, Busan 602-739, South Korea.
Kim
Su-Ryun
SR
Lee
Hak-Joong
HJ
Wee
Hee-Jun
HJ
Yoo
Mi-Ae
MA
Ock Oh
Sae
S
Baek
Sun-Yong
SY
Kim
Bong-Seon
BS
Kim
Jae-Bong
JB
Sik-Yoon
Bae
Soo-Kyung
SK
D001241:Aspirin / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015687:Cell Hypoxia / Q000187:drug effects; D015536:Down-Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D051550:I-kappa B Kinase; D001241:Aspirin