Selective suppression of Toll-like receptor 4 activation by chemokine receptor 4.
The response of Toll-like receptor 4 (TLR4) to lipopolysaccharide (LPS) is thought vital for resisting infection. Since aberrant TLR4 signaling may initiate inflammatory conditions such as the sepsis syndrome, we sought a component of normal cells that might provide local control of TLR4 activation. We found that antibodies that block chemokine receptor 4 (CXCR4) function enhanced TLR4 signaling, while increased expression of CXCR4 or addition of the CXCR4 ligand SDF-1 suppressed TLR4 signaling induced by LPS. These findings suggest that CXCR4 could exert local control of TLR4 and suggest the possibility of new therapeutic approaches to suppression of TLR4 function.
Kishore
Sandeep P
SP
Transplantation Biology, Mayo Clinic, 200 First Street SW, Medical Sciences 2-66, Rochester, MN 55905, USA.
Bungum
Marlo K
MK
Platt
Jeffrey L
JL
Brunn
Gregory J
GJ
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D017931:DNA Primers; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors