Dexmedetomidine inhibits the lipopolysaccharide-stimulated inflammatory response in microglia through the pathway involving TLR4 and NF-κB.
Xue-Yue ZhouJing LiuZhi-Peng XuQiang FuPei-Qi WangHong ZhangPublished in: The Kaohsiung journal of medical sciences (2019)
To investigate the effects of dexmedetomidine (DEX) on lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglia. BV2 microglial cells were treated with various concentrations of DEX (0, 1, 10, and 100 ng/mL) for 1 hour, and then incubated in the presence or absence of 0.1 μg/mL LPS for 24 hours. Cell viability was assessed by Cell Counting Kit-8 assays. The expression levels of IL-1β, IL-6, and TNF-α were determined using enzyme-linked immunosorbent assay (ELISA). The expressions of TLR4 and NF-кB were detected by western blotting. Moreover, BV2 microglial cells were transfected with small interfering RNA (siRNA) specific for TLR4 (si-TLR4 group) or negative control siRNA (si-NC group) for 24 hours, followed by exposing to 0.1 μg/mL LPS for 24 hours. TLR4, IL-1β, IL-6, and TNF-α expressions were detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR). There were no significant differences in cell viability with the different treatments. Compared with the control group, LPS markedly increased the release of IL-6, TNF-α, IL-1β, TLR4, and NF-κB, but these increases were significantly attenuated by pretreatment with 10 or 100 ng/mL DEX in a dose-dependent relationship, but not with 1 ng/mL DEX. Gene expression levels of IL-1β, IL-6, and TNF-α were obviously upregulated in si-NC group and si-TLR4 group when cells were exposed to 0.1 μg/mL LPS for 24 hours. Meanwhile, si-TLR4 group had significantly lower IL-1β, IL-6, and TNF-α expressions than si-NC group. The anti-inflammatory effects of DEX on LPS-induced BV2 microglia may be mediated through pathway involving TLR4 and NF-κB.
Keyphrases
- inflammatory response
- lps induced
- toll like receptor
- lipopolysaccharide induced
- gene expression
- induced apoptosis
- rheumatoid arthritis
- dna methylation
- room temperature
- oxidative stress
- anti inflammatory
- poor prognosis
- blood pressure
- immune response
- stem cells
- mesenchymal stem cells
- cell proliferation
- transcription factor
- mass spectrometry
- single cell
- endoplasmic reticulum stress
- spinal cord injury
- blood brain barrier
- bone marrow
- acute kidney injury
- cell therapy
- nucleic acid