MD-2 protein represents an excellent target for pharmacological inhibition of LPS-induced excessive immune response. From this point of view the protein MD-2 has not been studied yet. We demonstrated that curcumin binds into the hydrophobic pocket of MD-2. Binding of curcumin prevents the binding of LPS to MD-2, therefore, a signaling pathway of inflammatory response is inhibited. We also defined MD-2 as the target responsible for the already-known anti-inflammatory effect of curcumin, the main component of curcuma spices that are used in traditional medicine and nutrition.
COBISS.SI-ID: 3732762
Taxanes, particularly paclitaxel (taxol) and docetaxel (taxotere) are interesting to study signaling in the immune response of the organism to bacterial infection. It is known that paclitaxel, which is used in chemotherapy treatment, activates cells only through mouse receptor complex MD-2/TLR4 but not through human complex. We showed that the paclitaxel and docetaxel bind into the hydrophobic pocket of MD-2, where is the binding site of bacterial endotoxin LPS. Binding of taxanes to MD-2 inhibited the activation of human cells with LPS.
COBISS.SI-ID: 4065818
The hydrophobic pocket of MD-2 with internal free cysteine represents an excellent target for pharmacological inhibition of LPS-induced excessive inflammatory response. We tested compounds with high affinity to the hydrophobic pocket and with thiol-reactive group that could irreversibly inhibit LPS-dependent signaling pathway by binding to –SH group of free cysteine inside the pocket. We demonstrated a covalent binding of fluorescent compound N-pyrene maleimide. Drugs JTT-705 and auranofin which are already used in medicine for other indications efficiently inhibited LPS signaling pathway.
COBISS.SI-ID: 0000000