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Platelet-activating factor and endotoxin activate CCAAT/enhancer binding protein in rat small intestine. 2001

H Wang, and X Qu, and I G De Plaen, and W Hsueh
Department of Pathology, Children's Memorial Medical Center, Northwestern University Medical School, Chicago, Illinois, IL 60614, USA.

The transcription factor family CCAAT/enhancer binding proteins (C/EBP) is involved in inflammation via the regulation of the gene expression of various pro-inflammatory cytokines and proteins. PAF and endotoxin (lipopolysaccharide, LPS) are known agents causing intestinal inflammation and injury. In this study, we examined the binding activity of C/EBP isoforms in rat small intestine in response to PAF (1.5 microg kg(-1), i.v.) or LPS (5 mg kg(-1), i.v.). We found that C/EBP is constitutively active in normal small intestine, mainly as C/EBP-alpha and beta (C/EBP-beta>alpha). Both C/EBP-alpha and beta are localized in the intestinal epithelial cells: C/EBP-alpha mainly in the crypts, and C/EBP-beta in both villi and crypts, as well as in some lamina propria cells. Only minute amounts of C/EBP-delta were found. PAF rapidly upregulates the binding activity of C/EBP-alpha and beta within 30 min. The increase in C/EBP-alpha is prominent in the crypt cells, whereas the change of C/EBP-beta is more widespread. LPS also increases the binding activity of C/EBP-alpha and beta, and the response is slower than PAF. PAF synergizes with LPS to markedly activate all three subunits. The increase in C/EBP-alpha is transient, whereas the other two have a sustained elevation until 120 min. After challenge with PAF (but not LPS), small amounts of nuclear factor -kappaB (NF-kappaB) p50 and p65 subunits are found in the C/EBP-DNA binding complex, indicating cross-dimerization of the two transcription families. Pretreatment of rats with pyrrolidine dithiocarbamate (PDTC) suppresses LPS-, but not PAF-, induced NF-kappaB and C/EBP binding activity, and significantly increases the C/EBP-delta subunit in LPS- or PAF-induced C/EBP complex. These results suggest that PAF and LPS activate intestinal C/EBP in vivo, probably via different pathways.

UI MeSH Term Description Entries
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D007421 Intestine, Small The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM. Small Intestine,Intestines, Small,Small Intestines
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008297 Male Males
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004731 Endotoxins Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. Endotoxin

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