PMID- 8863511 OWN - NLM STAT- MEDLINE DCOM- 19961202 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 67 IP - 5 DP - 1996 Nov TI - Interleukin-1 beta and tumor necrosis factor-alpha induce expression of alpha 1-antichymotrypsin in human astrocytoma cells by activation of nuclear factor-kappa B. PG - 2039-44 AB - The protease inhibitor alpha 1-antichymotrypsin (ACT) has been suggested to be involved in the etiology of Alzheimer's disease (AD). Increased levels of ACT have been found in serum and brains of AD patients, and ACT has been proposed to regulate beta-amyloid fibril formation in vitro. To gain insight into the regulation of ACT in the brain, we investigated the signal transduction pathways involved in ACT gene expression and protein synthesis in the human astrocytoma cell line U373. This cell line has previously been shown to respond with strong ACT synthesis on stimulation with interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF alpha). Here, we describe that both IL-1 beta and TNF alpha activate the transcription factor nuclear factor-kappa B (NF-kappa B) via production of reactive oxygen intermediates resulting in ACT expression. In addition, we show that neither protein kinase C nor protein kinase A is involved in IL-1 beta- or TNF alpha-induced ACT expression. These results suggest that activation of NF-kappa B may be one possible cause of increased ACT levels in AD and provide a basis for the development of drugs used for the modulation of inflammatory processes occurring in AD. FAU - Lieb, K AU - Lieb K AD - Abteilung Psychiatrie und Psychotherapie, Universitat Freiburg, Germany. FAU - Fiebich, B L AU - Fiebich BL FAU - Schaller, H AU - Schaller H FAU - Berger, M AU - Berger M FAU - Bauer, J AU - Bauer J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Interleukin-1) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (alpha 1-Antichymotrypsin) RN - 1F7A44V6OU (Colforsin) RN - 63X7MBT2LQ (Bucladesine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Astrocytoma/*metabolism MH - Blotting, Northern MH - Bucladesine/pharmacology MH - Cell Line MH - Colforsin/pharmacology MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Humans MH - Interleukin-1/*pharmacology MH - NF-kappa B/*metabolism MH - RNA, Messenger/biosynthesis MH - Recombinant Proteins/pharmacology MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transcription, Genetic/*drug effects MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/*pharmacology MH - alpha 1-Antichymotrypsin/*biosynthesis EDAT- 1996/11/01 00:00 MHDA- 1996/11/01 00:01 CRDT- 1996/11/01 00:00 PHST- 1996/11/01 00:00 [pubmed] PHST- 1996/11/01 00:01 [medline] PHST- 1996/11/01 00:00 [entrez] AID - 10.1046/j.1471-4159.1996.67052039.x [doi] PST - ppublish SO - J Neurochem. 1996 Nov;67(5):2039-44. doi: 10.1046/j.1471-4159.1996.67052039.x.