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Biological activity of an LPS-like molecule extracted from the freshwater cyanobacterium Oscillatoria Planktothrix FP1

signalling dataset

We obtained data on the biological activity of an LPS-like molecule extracted from the freshwater cyanobacterium Oscillatoria Planktothrix FP1 that we named CyP. We found that CyP acts as a potent and selective antagonist of bacterial LPS. CyP did not induce any detectable response in human DCs and competitively inhibited LPS binding to the extracellular domain of TLR4. Addition of CyP together with LPS completely inhibited both MyD88- and TRIF-dependent pathways and suppressed the whole LPS-induced gene transcription program. CyP was effective in protecting mice from endotoxin shock in spite of a lower capacity to inhibit LPS stimulation of mouse DCs. Remarkably, delayed addition of CyP to DCs responding to LPS strongly inhibited signaling and cytokine production by immediate down-regulation of inflammatory cytokine mRNAs, while not affecting other aspects of DC maturation such as expression of MHC, costimulatory molecules and CCR7. These results open promising perspectives for the use of CyP as a therapeutic agent able to modulate innate and adaptive immune responses and reveal the requirement of sustained TLR4 stimulation for induction of cytokine gene expression in human DCs.




created over 8 years ago (2 March 2009)    last modified over 5 years ago (25 June 2012)   [ RDF Rdf ]   [ RelFinder Relfinder ]