Environmental conditioning in the control of macrophage thrombospondin-1 production.
Thrombospondin-1 (TSP-1) is a multifunctional protein which is secreted into the extracellular matrix during inflammation, where it modulates numerous components of the immune infiltrate. Macrophages are a source of TSP-1, which they produce in response to TLR4 mediated signals. Their production of TSP-1 is regulated by environmental signals that establish a threshold for the level of protein secretion that can be induced by LPS stimulation. Th1 and Th2 cytokines raise this threshold which leads to less TSP-1 production, while signals that promote the generation of regulatory macrophages lower it. TSP-1 plays no direct role in the regulation of its own secretion. In vivo in uveitis, in the presence of TLR-4 ligands, TSP-1 is initially produced by recruited macrophages but this decreases in the presence of inflammatory cytokines. The adaptive immune system therefore plays a dominant role in regulating TSP-1 production in the target organ during acute inflammation.
School of Clinical Sciences, University of Bristol, Bristol, UK.
Jezrom B
JB
Fordham
Jing
J
Hua
Sarah R
SR
Morwood
Lauren P
LP
Schewitz-Bowers
David A
DA
Copland
Andrew D
AD
Dick
Lindsay B
LB
Nicholson
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010529:Peritoneal Cavity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019700:Thrombospondin 1 / Q000096:biosynthesis*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014605:Uveitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D008070:Lipopolysaccharides; D019700:Thrombospondin 1; D051197:Toll-Like Receptor 4; D000241:Adenosine; D015232:Dinoprostone