PMID- 7797472 OWN - NLM STAT- MEDLINE DCOM- 19950731 LR - 20210210 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 270 IP - 25 DP - 1995 Jun 23 TI - Platelet-activating factor induces NF-kappa B activation through a G protein-coupled pathway. PG - 14928-34 AB - The capability of platelet-activating factor (PAF) to induce transcription factor activation was examined. In stably transfected Chinese hamster ovary cells expressing the PAF receptor (CHO-PAFR), PAF stimulation resulted in the nuclear expression of a DNA binding activity with specificity to the kappa B sequence. The p50 and p65 proteins, constituents of the prototypic nuclear factor kappa B (NF-kappa B), were identified as components of the DNA protein complexes by antipeptide antibodies in gel supershift as well as UV cross-linking experiments. PAF induced an initial decrease and subsequent increase of cytoplasmic I kappa B alpha levels, accompanied by up-regulation of the I kappa B alpha messenger RNA, a feature of NF-kappa B activation. PAF-induced kappa B binding activity was detected within 15 min after agonist stimulation, peaked at 30-40 min, and remained detectable by 2.5 h. SR 27417, a PAF receptor antagonist, blocked PAF-induced kappa B binding activity but not that induced by tumor necrosis factor-alpha (TNF alpha). Cholera toxin treatment markedly reduced PAF-induced kappa B binding activity, whereas pertussis toxin had no significant inhibitory effect. Neither of the two toxins affected the kappa B binding activity induced by TNF alpha in the same cells. In addition to the CHO-PAFR cells, PAF stimulated kappa B binding activity in the murine P388D1 macrophage and the human ASK.0 B cell lines that express endogenous PAF receptors. These results imply a potential role of PAF in the regulation of gene expression through a G protein-coupled transcription factor activation pathway. FAU - Kravchenko, V V AU - Kravchenko VV AD - Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA. FAU - Pan, Z AU - Pan Z FAU - Han, J AU - Han J FAU - Herbert, J M AU - Herbert JM FAU - Ulevitch, R J AU - Ulevitch RJ FAU - Ye, R D AU - Ye RD LA - eng GR - AI15136/AI/NIAID NIH HHS/United States GR - AI33503/AI/NIAID NIH HHS/United States GR - GM37696/GM/NIGMS NIH HHS/United States GR - etc. PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (NF-kappa B) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Platelet Activating Factor) RN - 0 (Platelet Membrane Glycoproteins) RN - 0 (Receptors, Cell Surface) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (platelet activating factor receptor) RN - 9007-49-2 (DNA) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites MH - CHO Cells MH - Cell Line MH - Cell Nucleus/drug effects/metabolism MH - Cricetinae MH - DNA/chemistry/metabolism MH - GTP-Binding Proteins/*metabolism MH - Gene Expression MH - Humans MH - Kinetics MH - Macrophages MH - Mice MH - Molecular Sequence Data MH - NF-kappa B/*biosynthesis/metabolism MH - Oligodeoxyribonucleotides MH - Platelet Activating Factor/metabolism/*pharmacology MH - Platelet Membrane Glycoproteins/biosynthesis/*physiology MH - Promoter Regions, Genetic MH - *Receptors, Cell Surface MH - *Receptors, G-Protein-Coupled MH - Recombinant Proteins/biosynthesis/metabolism MH - Transfection MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1995/06/23 00:00 MHDA- 1995/06/23 00:01 CRDT- 1995/06/23 00:00 PHST- 1995/06/23 00:00 [pubmed] PHST- 1995/06/23 00:01 [medline] PHST- 1995/06/23 00:00 [entrez] AID - S0021-9258(18)90485-0 [pii] AID - 10.1074/jbc.270.25.14928 [doi] PST - ppublish SO - J Biol Chem. 1995 Jun 23;270(25):14928-34. doi: 10.1074/jbc.270.25.14928.