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• W1566795317 abstract "Abstract We investigated whether angiotensin (ANG) II and its receptors contribute to lipopolysaccharide (LPS)‐induced microglial activation through activation of the proinflammatory transcription factors nuclear factor κB (NF‐κB) and activator protein‐1 (AP‐1). Using primary microglial cell cultures, we examined whether losartan [ANG type 1 receptor (AT 1 ) antagonist] alters the effects of LPS on: the production of interleukin‐1 (IL‐1) and nitric oxide, cell morphology, and NF‐κB and AP‐1 activities. Reverse transcription‐polymerase chain reaction revealed that LPS‐stimulated microglial cells exhibited marked mRNA expression for AT 1 , ANG type 2 receptor (AT 2 ) and the ANG II precursor angiotensinogen, whereas non‐stimulated microglial cells expressed only those for AT 2 and angiotensinogen. We further demonstrated marked peptide/protein expression for AT 1 and ANG II in LPS‐activated microglial cells. LPS (100 ng/mL)‐stimulated microglial cells showed increased concentrations of IL‐1 and nitrite (a relatively stable metabolite of nitric oxide), and increased expression of IL‐1 mRNA as well as a morphological change from an amoeboid shape to a multipolar (mostly bipolar but sometimes tripolar) rod shape. These effects were all significantly inhibited by losartan treatment (10 −5 m or less). NF‐κB and AP‐1 activities were enhanced in LPS‐stimulated microglial cells, effects that were significantly suppressed by losartan (10 −5 m ). ANG II application enhanced the LPS‐induced increases in IL‐1 and nitrite concentrations, as well as the LPS‐induced morphological changes and AP‐1 activation, and these enhancements were inhibited by losartan (10 −5 m ). These results suggest that endogenous ANG II enhances LPS‐induced microglial activities through stimulation of the microglial AT 1 , which itself evokes activation of the transcription factors NF‐κB and AP‐1." @default.
• W1566795317 created "2016-06-24" @default.
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• W1566795317 date "2008-01-01" @default.
• W1566795317 modified "2023-10-10" @default.
• W1566795317 title "Angiotensin type 1 receptor antagonist inhibits lipopolysaccharide-induced stimulation of rat microglial cells by suppressing nuclear factor κB and activator protein-1 activation" @default.
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• W1566795317 doi "https://doi.org/10.1111/j.1460-9568.2007.06014.x" @default.
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