CD200Fc reduces TLR4-mediated inflammatory responses in LPS-induced rat primary microglial cells via inhibition of the NF-κB pathway
L Jiang, F Xu, W He, L Chen, H Zhong, Y Wu… - Inflammation …, 2016 - Springer
L Jiang, F Xu, W He, L Chen, H Zhong, Y Wu, S Zeng, L Li, M Li
Inflammation research, 2016•SpringerObjective Based on recent information, CD200Fc, a CD200R1 agonist, could attenuate the
inflammatory response of microglial cells in autoimmune diseases and neuro-degeneration.
However, the exact molecular mechanisms responsible for the anti-inflammatory activity of
CD200Fc in microglial cells have not been elucidated. In the present study, we investigated
the anti-inflammatory effects and the molecular mechanisms of CD200Fc in
lipopolysaccharide (LPS)-stimulated rat primary microglial cells. Methods The cell viability …
inflammatory response of microglial cells in autoimmune diseases and neuro-degeneration.
However, the exact molecular mechanisms responsible for the anti-inflammatory activity of
CD200Fc in microglial cells have not been elucidated. In the present study, we investigated
the anti-inflammatory effects and the molecular mechanisms of CD200Fc in
lipopolysaccharide (LPS)-stimulated rat primary microglial cells. Methods The cell viability …
Objective
Based on recent information, CD200Fc, a CD200R1 agonist, could attenuate the inflammatory response of microglial cells in autoimmune diseases and neuro-degeneration. However, the exact molecular mechanisms responsible for the anti-inflammatory activity of CD200Fc in microglial cells have not been elucidated. In the present study, we investigated the anti-inflammatory effects and the molecular mechanisms of CD200Fc in lipopolysaccharide (LPS)-stimulated rat primary microglial cells.
Methods
The cell viability was measured by MTT assay. The LPS-induced cytokines release (IL-1β, IL-6, TNF-α, iNOS, MCP-1, and COX-2) was monitored by ELISA or real-time PCR, while NF-κB-related signals (MyD88, p-TAK1, TRIF, p-TBK1, p-IRF3, p-IκB, and NF-κB-P65) were assessed by real-time PCR, western blot and/or Immunofluorescent staining.
Results
CD200Fc and/or LPS exerted no significant cytotoxicity on microglial cells. LPS reduced the CD200R1 expression in microglial cells, and this effect was attenuated by CD200Fc. In addition, CD200Fc inhibited LPS-induced expression of TLR4 and its adapter molecules (MyD88 and p-TAK1, TRIF, p-TBK1, and p-IRF3), and abolished its interactions with MyD88, TAK1, and TRIF in microglial cells. CD200Fc also attenuated LPS-induced protein expression of p-IκB and NF-κB-P65 translocation to nucleus in microglial cells. Moreover, CD200Fc suppressed the LPS-induced release of inflammatory mediators in microglial cells, including IL-1β, IL-6, TNF-α, iNOS, MCP-1, and COX-2.
Conclusion
These results indicated that CD200Fc displayed an anti-inflammatory effect in LPS-induced microglial cells by blocking TLR4-mediated NF-κB activation.
Springer