Prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) synthesis is regulated by conjugated linoleic acids (CLA) in human macrophages. 2009

E Stachowska, and B Dolegowska, and V Dziedziejko, and M Rybicka, and M Kaczmarczyk, and J Bober, and M Rac, and B Machalinski, and D Chlubek
Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, ul. Zolnierska 48, Szczecin, Poland. ewast@sci.pam.szczecin.pl

Conjugated linoleic acid (CLAs) are positional and geometric isomers of linoleic acid with have a potential anti-atherosclerotic and anti-inflammation properties. Metabolites of arachidonic acid--prostaglandins and thromboxans--are endogenous mediators of inflammation. Prostaglandin E(2) and thromboxan A(2) which are a products of two izoformes of cyclooxygenases (COX-1 and COX-2) in macrophages, play an important role in this process. COX-1 is a constitutive enzyme, whereas the COX-2 is inducible and its amount in the cell rapidly increases during inflammation (e.g. via NF kappaB pathway). The aim of the study was to test the effect of CLAs on cyclooxygenases (COX-1 and COX-2) activity, their mRNA expression and protein content in macrophages. Additionally the active form of the kappaB (NF kappaB) transcription factor was measured. For the experiments monocytes from monocytic cell line (THP-1) and from human venous blood were used. Monocytes were differentiated to macrophages and cultured with 30 muM CLAs or linoleic acid for 48 h. The COX-1 and COX-2 products - PGE(2) and TXB(2), were measured by ELISA method. The enzymes (COX-s) activity were estimated by spectroscopic method. mRNA expression and protein analysis were analysed by real-time PCR and Western blot technique. In macrophages cultured with CLAs reduction of TXB(2) and PGE(2) concentration was observed. Significant change in COX-2 expression in cells cultured with trans-10, cis-12 CLA (in macrophages obtained from peripheral blood) was observed. COX-1 inhibition was resulting from competition of CLA and linoleic acid with arachidonic acid.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013928 Thromboxane A2 An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS). Rabbit Aorta Contracting Substance,A2, Thromboxane
D015153 Blotting, Western Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes. Immunoblotting, Western,Western Blotting,Western Immunoblotting,Blot, Western,Immunoblot, Western,Western Blot,Western Immunoblot,Blots, Western,Blottings, Western,Immunoblots, Western,Immunoblottings, Western,Western Blots,Western Blottings,Western Immunoblots,Western Immunoblottings
D015232 Dinoprostone The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D015971 Gene Expression Regulation, Enzymologic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. Enzymologic Gene Expression Regulation,Regulation of Gene Expression, Enzymologic,Regulation, Gene Expression, Enzymologic

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