Down-regulation of the expression of rat inhibitor-of-apoptosis protein-1 and -3 during transforming growth factor-beta1-mediated apoptosis in rat brain microglia.
Transforming growth factor (TGF)-beta1 is a key regulator of brain response to injury and inflammation. It exerts anti-inflammatory roles by inhibiting microglial proliferation and free radical induction. TGF-beta1 is known to induce apoptotic cell death of microglia in a Bcl-2-independent pathway. The purpose of this study was to examine detailed mechanisms of TGF-beta1-induced microglial apoptosis. Assays for cell viability and DNA fragmentation demonstrated that TGF-beta1 induced apoptotic cell death in primary rat microglial cultures. Reverse transcription (RT)-PCR analysis showed that primary microglial cells expressed mRNAs for rat inhibitor-of-apoptosis protein (RIAP)-1 and RIAP-3 under normal culture conditions and that treatment with TGF-beta1 resulted in a significant reduction in the amounts of RIAP-1 and RIAP-3 mRNAs. Because IAPs are potent suppressor of apoptotic cell death, decrease in IAP expression might provide an important regulatory function in TGF-beta1-mediated microglial death and in attenuation of excessive microglial activation in pathological conditions.
Jung
Bomi
B
Graduate School of East-West Medical Science, Kyung Hee University, Yong-In 499-701, Korea.
Kim
Mi-Ok
MO
Yun
Su-Jin
SJ
Lee
Eunjoo H
EH
D000818:Animals; D017209:Apoptosis; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D018929:Cell Culture Techniques; D053938:DNA Fragmentation; D015536:Down-Regulation; D051034:Inhibitor of Apoptosis Proteins; D017628:Microglia / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D051034:Inhibitor of Apoptosis Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C494837:Xiap protein, rat; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; C494836:Birc3 protein, rat