Chemokine-enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9.
The increased migration of peripheral blood mononuclear cells (PBMNCs) across a fibronectin (FN) matrix in response to the chemokines RANTES, MIP-1 alpha and MCP-1 is antagonized by interferon-beta-1b (IFN beta-1b). MCP-1 treatment of PBMNCs elevates their mRNA level and secretion of a matrix degrading enzyme, matrix metalloproteinase (MMP)-9, which is abrogated by IFN beta-1b. The clinical benefits of IFN beta-1b treatment in multiple sclerosis patients may in part be a result of this drug's ability to decrease the migration of PBMNCs in spite of a chemotactic gradient. Furthermore, the elevation of MMP-9 production by PBMNCs may be an important mechanism of action of chemokines.
Stuve
O
O
Department of Neurology and Neurosurgery, McGill University, Montreal, Que., Canada.
Chabot
S
S
Jung
S S
SS
Williams
G
G
Yong
V W
VW
D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D018925:Chemokines; D019402:Macrophage Inflammatory Proteins; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D000068576:Interferon beta-1b; D016899:Interferon-beta; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D000068556:Interferon beta-1a