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Telmisartan ameliorates inflammation in various brain disorders through angiotensin II type 1 receptor (AT1) blockade and peroxisome proliferator-activated receptor gamma (PPARγ) activation. Soluble β-amyloid oligomers (AβOs) play a causative role in neuronal dysfunction and memory loss in Alzheimer's disease. In addition to directly targeting neurons, AβOs may also activate microglia to trigger toxic proinflammatory responses. Here, we investigated whether and how telmisartan ameliorates inflammatory responses in AβO-stimulated microglia. A mouse-derived BV2 microglial cell line lacking AT1 expression was selected as an in vitro model. Telmisartan not only inhibited AβO-induced proinflammatory interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) expression, but also increased anti-inflammatory IL-10 expression, which was not affected by AβO stimulation. Telmisartan also inhibited AβO-induced nuclear factor (NF)-κB activity and phosphorylation of Akt and ERK, two upstream regulators of NF-κB activation. These anti-inflammatory effects were antagonized by PPARγ inhibitor GW9662. In addition, telmisartan increased the expression of PTEN (phosphate and tensin homolog deleted on chromosome 10), a lipid and protein phosphatase; PPARγ inhibitor GW9662 reversed this effect, indicating that telmisartan-induced PTEN expression is PPARγ dependent. The PTEN inhibitor blocked the effects of telmisartan on Akt and ERK phosphorylation, NF-κB transcriptional activity, and IL-1β and TNF-α production, but failed to reverse IL-10 expression. This data indicates that telmisartan-induced IL-10 expression is PPARγ-dependent but PTEN-independent. Altogether, telmisartan ameliorated AβO-induced microglial inflammation by inhibiting NF-κB-mediated proinflammatory cytokine expression via the PPARγ/PTEN pathways and by increasing PPARγ-mediated anti-inflammatory IL-10 expression. Telmisartan may present a promising therapy for the treatment of AβO pathology.
This article was published in the following journal.
Name: Biochemical pharmacology
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One of the PPAR nuclear transcription factors.
A lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.
Abnormally high temperature intentionally induced in living things regionally or whole body. It is most often induced by radiation (heat waves, infra-red), ultrasound, or drugs.
A subtype of bradykinin receptor that is induced in response to INFLAMMATION. It may play a role in chronic inflammation and has a high specificity for KININS lacking the C-terminal ARGININE such as des-Arg(10)-kallidin and des-Arg(9)-bradykinin. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.
Artificially induced UTERINE CONTRACTION. Generally, LABOR, OBSTETRIC is induced with the intent to cause delivery of the fetus and termination of pregnancy.
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Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...