PMID- 16545883 OWN - NLM STAT- MEDLINE DCOM- 20060921 LR - 20191210 IS - 0168-1702 (Print) IS - 0168-1702 (Linking) VI - 117 IP - 2 DP - 2006 May TI - Stimulation of interferon-beta gene expression by human cytomegalovirus via nuclear factor kappa B and phosphatidylinositol 3-kinase pathway. PG - 209-14 AB - Infection of human foreskin fibroblast (HFF) cells with human cytomegalovirus (HCMV) induces the secretion of soluble factors including interferon (IFN)-beta that stimulates human leukocyte antigen (HLA) class I expression. In this study, the mechanism of IFN-beta induction by HCMV was investigated. In HCMV-infected HFF cells, IFN-beta secretion increased at 6h post infection (h.p.i.). Reverse transcription polymerase chain reaction (RT-PCR) analysis using ultra violet (UV)-inactivated HCMV indicated that viral gene expression is not necessary for the stimulation of IFN-beta. Stimulation of IFN-beta by HCMV infection was not blocked by cycloheximide, an inhibitor of protein synthesis, further suggesting that the expression of HCMV genes is not required for the stimulation of IFN-beta gene transcription. IFN-beta may be produced from virus-infected cells as an inflammatory response and nuclear factor kappa B (NF-kappaB) plays a central role in inflammatory response. HCMV failed to induce the IFN-beta expression, when the virus-infected cells were treated with pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, or LY294002 and wortmannin, inhibitors of phosphatidylinositol 3-kinase (PI3-K). The result suggests that PI3-K and/or NF-kappaB may be related with the induction pathway of IFN-beta by HCMV. FAU - Lee, Gyu Cheol AU - Lee GC AD - Division of Life Sciences, College of Natural Sciences, and Biotechnology Research Institute, Chungbuk National University, 12 Gaeshindong, Cheongju, Chungbuk 361-763, South Korea. chlee@chungbuk.ac.kr FAU - Yi, Hyun Ah AU - Yi HA FAU - Lee, Chan Hee AU - Lee CH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060320 PL - Netherlands TA - Virus Res JT - Virus research JID - 8410979 RN - 0 (Androstadienes) RN - 0 (Enzyme Inhibitors) RN - 0 (NF-kappa B) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Pyrrolidines) RN - 0 (RNA, Messenger) RN - 0 (RNA, Viral) RN - 0 (Thiocarbamates) RN - 25769-03-3 (pyrrolidine dithiocarbamic acid) RN - 77238-31-4 (Interferon-beta) RN - 98600C0908 (Cycloheximide) RN - XVA4O219QW (Wortmannin) SB - IM MH - Androstadienes/pharmacology MH - Cell Line MH - Cycloheximide/pharmacology MH - Cytomegalovirus/*immunology MH - Enzyme Inhibitors/pharmacology MH - Fibroblasts/virology MH - *Gene Expression MH - Humans MH - Interferon-beta/*biosynthesis/*genetics MH - NF-kappa B/antagonists & inhibitors/*physiology MH - Phosphatidylinositol 3-Kinases/*physiology MH - Phosphoinositide-3 Kinase Inhibitors MH - Protein Synthesis Inhibitors/pharmacology MH - Pyrrolidines/pharmacology MH - RNA, Messenger/analysis MH - RNA, Viral/analysis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Thiocarbamates/pharmacology MH - Transcription, Genetic MH - Wortmannin EDAT- 2006/03/21 09:00 MHDA- 2006/09/22 09:00 CRDT- 2006/03/21 09:00 PHST- 2005/01/18 00:00 [received] PHST- 2005/08/14 00:00 [revised] PHST- 2005/08/19 00:00 [accepted] PHST- 2006/03/21 09:00 [pubmed] PHST- 2006/09/22 09:00 [medline] PHST- 2006/03/21 09:00 [entrez] AID - S0168-1702(05)00268-6 [pii] AID - 10.1016/j.virusres.2005.08.018 [doi] PST - ppublish SO - Virus Res. 2006 May;117(2):209-14. doi: 10.1016/j.virusres.2005.08.018. Epub 2006 Mar 20.