Journal: Journal of cellular and molecular medicine
Article Title: 25-Hydroxycholesterol protects against acute lung injury via targeting MD-2.
doi: 10.1111/jcmm.13820
Figure Lengend Snippet: FIGURE 6 Proposed model of 25HC preventing LPS‐induced TLR4 signalling pathway. LPS binding to MD2 promotes the dimerization of TLR4/MD‐2. The conformational changes in the TLR4 induce the recruitment of intracellular adaptor proteins to activate the downstream signalling pathway. The MyD88‐dependent pathway involves activation of MAPK cascades and IKK (IκB kinase). Phosphorylation of IKKs leads to degradation of IκBα and the release of NF‐κB. Transcription factors such as NF‐κB, AP‐1 and etc. participate in driving gene expression of proinflammatory cytokines. The activated PI3K/Akt in the downstream of TLR4 induces nuclear translation of NF‐κB. 25HC could directly interact with MD2 to prevent LPS‐induced activation of Akt and NF‐κB signal pathway
Article Snippet: Recombinant human MD‐2 (rhMD‐2) protein was obtained from R&D Systems (Minneapolis, MN, USA).
Techniques: Binding Assay, Activation Assay, Phospho-proteomics, Gene Expression