title: GM-CSF activates RhoA, integrin and MMP expression in human monocytic cells.
abstract: Monocyte migration is one of the key events occurring in the early stage of atherosclerosis. This process includes monocytic adhesion to and penetration through the arterial intima. In such an environment, many factors stimulate the monocytes to enhance integrin activation and extracellular matrix degradation. To investigate the coordinative operation of these two events in relation to monocyte migration, we paid particular attention to the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on monocytes in terms of RhoA activation and matrix metalloproteinase (MMP) expression. RhoA and integrin clustering were activated by GM-CSF, monocyte chemoattractant protein-1 (MCP-1) and platelet-derived growth factor-BB (PDGF-BB) in human monocytic cell lines. Furthermore, enhancement of migration was observed with stimulation by MCP-1 and PDGF-BB. Granulocyte-macrophage colony-stimulating factor did not enhance the migration, even though it activated RhoA and integrin. However, GM-CSF is known to stimulate monocytes to express MCP-1, suggesting the presence of an indirect mechanism for GM-CSF-mediated migratory activity. In contrast, only GM-CSF enhanced the expression of MMP-1 and MMP-9. These results provide evidence that GM-CSF has multiple functions enhancing monocytic migration via RhoA and integrin activation, and via MMP expression.
authors.affiliation: Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Kohno
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
authors.forename: Cintana
authors.initials: C
authors.lastname: Cirathaworn
authors.forename: Shohei
authors.initials: S
authors.lastname: Shimajiri
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tawara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
mesh_terms: D000077214:Becaplermin; D015152:Blotting, Northern; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology; D017930:Genes, Reporter; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D008156:Luciferases; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C066737:RHOA protein, human; D000077214:Becaplermin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008156:Luciferases; D020782:Matrix Metalloproteinases; D020742:rhoA GTP-Binding Protein