PMID- 18084608 OWN - NLM STAT- MEDLINE DCOM- 20080225 LR - 20211020 IS - 1476-5586 (Electronic) IS - 1522-8002 (Print) IS - 1476-5586 (Linking) VI - 9 IP - 12 DP - 2007 Dec TI - RNA interference of interferon regulatory factor-1 gene expression in THP-1 cell line leads to Toll-like receptor-4 overexpression/activation as well as up-modulation of annexin-II. PG - 1012-20 AB - Interferon regulatory factor-1 (IRF-1) is a candidate transcription factor for the regulation of the Toll-like receptor-4 (TLR-4) gene. Using a small interfering RNA-based (siRNA) process to silence IRF-1 gene expression in the leukemic monocytic cell line THP-1, we investigated whether such a modulation would alter TLR-4 expression and activation status in these cells. The siIRF-1 cells expressed elevated levels of TLR-4 mRNA and protein compared to controls by 90% and 77%, respectively. ICAM.1 protein expression and apoptosis levels were increased by 8.35- and 4.25-fold, respectively. The siIRF-1 cells overexpressed Bax mRNA compared to controls. Proteomic analysis revealed upmodulation of the Annexin-II protein in siIRF-1 THP-1 cells. Myelodysplastic syndrome (MDS) patients with an absence of full-length IRF-1 mRNA also overexpressed Annexin-II. It is plausible that this overexpression may lead to the activation of TLR-4 contributing to the increased apoptosis characterizing MDS. FAU - Maratheftis, Christos I AU - Maratheftis CI AD - Department of Pathophysiology, School of Medicine, National University of Athens, Athens, Greece. FAU - Giannouli, Stavroula AU - Giannouli S FAU - Spachidou, Maria P AU - Spachidou MP FAU - Panayotou, George AU - Panayotou G FAU - Voulgarelis, Michael AU - Voulgarelis M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neoplasia JT - Neoplasia (New York, N.Y.) JID - 100886622 RN - 0 (ANXA2 protein, human) RN - 0 (Annexin A2) RN - 0 (BAX protein, human) RN - 0 (Interferon Regulatory Factor-1) RN - 0 (RNA, Messenger) RN - 0 (RNA, Small Interfering) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (bcl-2-Associated X Protein) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Amino Acid Sequence MH - Annexin A2/*biosynthesis/genetics MH - Apoptosis MH - Bone Marrow Cells/metabolism/pathology MH - Cells, Cultured/drug effects/metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Intercellular Adhesion Molecule-1/biosynthesis/genetics MH - Interferon Regulatory Factor-1/*antagonists & inhibitors/genetics/physiology MH - Leukemia, Promyelocytic, Acute/metabolism/pathology MH - Molecular Sequence Data MH - Monocytes/*metabolism MH - Myelodysplastic Syndromes/metabolism/pathology MH - Protein Structure, Tertiary MH - *RNA Interference MH - RNA, Messenger/genetics MH - RNA, Small Interfering/pharmacology MH - Toll-Like Receptor 4/*biosynthesis/genetics MH - Transfection MH - bcl-2-Associated X Protein/biosynthesis/genetics PMC - PMC2134898 OTO - NOTNLM OT - Annexin II OT - IRF-1 OT - RNAi OT - TLR-4 OT - myelodysplastic syndrome EDAT- 2007/12/18 09:00 MHDA- 2008/02/26 09:00 PMCR- 2007/12/01 CRDT- 2007/12/18 09:00 PHST- 2007/07/25 00:00 [received] PHST- 2007/10/08 00:00 [revised] PHST- 2007/10/09 00:00 [accepted] PHST- 2007/12/18 09:00 [pubmed] PHST- 2008/02/26 09:00 [medline] PHST- 2007/12/18 09:00 [entrez] PHST- 2007/12/01 00:00 [pmc-release] AID - 07640 [pii] AID - 10.1593/neo.07640 [doi] PST - ppublish SO - Neoplasia. 2007 Dec;9(12):1012-20. doi: 10.1593/neo.07640.