Selective induction of matrix metalloproteinases by Borrelia burgdorferi via toll-like receptor 2 in monocytes.
Regulation of secretion of matrix metalloproteinase (MMP) underlies the basis of numerous physiological and pathological processes in multicellular organisms. The Toll receptor family, which is conserved from Drosophila species to humans, mediates pattern recognition of a diversity of ligands involved in morphogenesis and innate immunity. Here, we show that secretion of MMP-9 is selectively induced through Toll-like receptor (TLR) 2 in human and murine monocytic cells stimulated with Borrelia burgdorferi. Secretion of MMP-1 was shown to be stimulated through a pathway other than TLR2, under identical conditions. Analysis of nuclear extracts indicated that activator protein (AP)-1 was reduced in TLR2-neutralized monocytic cells, suggesting that AP-1 plays a role in the transcriptional activation of MMP-9 through TLR2. The specific induction of MMP-9 through TLR2 provides direct evidence of a new role for this ancient receptor family in regulating secretion of MMPs and demonstrates evolutionary convergence between invertebrate morphogenesis and the vertebrate innate immune system.
Gebbia
Joseph A
JA
Center for Infectious Diseases, Centers for Molecular Medicine, and State of New York Department of Health, Stony Brook University, Stony Brook, New York, USA.
Coleman
James L
JL
Benach
Jorge L
JL
D000818:Animals; D025065:Borrelia burgdorferi / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D017737:Macrophages, Peritoneal; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1