[Angiotensin II induces toll-like receptor 4 expression and myeloperoxidase activity in RAW264.7 cells]. 2008

Yuan-yuan Ji, and Zhi-dong Wang, and Jun-tian Liu, and Na Liu
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.

OBJECTIVE To investigate the effects of angiotensin II (Ang II) on mRNA and protein expressions of toll-like receptor 4 (TLR4) and myeloperoxidase (MPO) activity in RAW264.7 cells, and explore its pro-inflammatory and pro-atherosclerotic mechanisms. METHODS Murine RAW264.7 cells were cultured and stimulated with different concentrations (1, 10, 100 and 1,000 nmol/L) of Ang II or LPS (100 microg/L) for 24 h. TLR4 mRNA levels were analyzed by RT-PCR, and TLR4 protein expression was measured by Western blot. MPO activity in the supernatant was assayed with colorimetry. Then, the cells were pretreated with TLR4 blocker (1 and 5 mg/L) for 1 h prior to stimulation with 100 nmol/L Ang II for 24 h, and MPO activity in the supernatant was detected. RESULTS Ang II increased mRNA and protein expressions of TLR4 in RAW264.7 cells in concentration-dependent manner (P<0.01), and LPS also induced mRNA and protein expressions of TLR4 in RAW264.7 cells (P<0.01). In addition, Ang II concentration-dependently elevated MPO activity in RAW264.7 cells (P<0.01), and LPS also enhanced MPO activity of RAW264.7 cells (P<0.01), but the TLR4 blocker significantly antagonized the effect of Ang II on MPO activity (P<0.01). CONCLUSIONS Ang II upregulates TLR4 expressions, and induces MPO secretion via TLR4 in RAW264.7 cells, which mediate the pro-inflammatory effect of Ang II to contribute formation and development of atherosclerosis.

UI MeSH Term Description Entries
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
D009195 Peroxidase A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. Myeloperoxidase,Hemi-Myeloperoxidase,Hemi Myeloperoxidase
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D000804 Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS. Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
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
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions
D051197 Toll-Like Receptor 4 A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA. TLR4 Receptor,Toll-4 Receptor,Receptor, TLR4,Toll 4 Receptor,Toll Like Receptor 4
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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