title: Transforming growth factor-beta1 regulates macrophage migration via RhoA.
abstract: Brief treatment with transforming growth factor (TGF)-beta1 stimulated the migration of macrophages, whereas long-term exposure decreased their migration. Cell migration stimulated by TGF-beta1 was markedly inhibited by 10 mug/mL Tat-C3 exoenzyme. TGF-beta1 increased mRNA and protein levels of macrophage inflammatory protein (MIP)-1alpha in the initial period, and these effects also were inhibited by 10 mug/mL Tat-C3 and a dominant-negative (DN)-RhoA (N19RhoA). Cycloheximide, actinomycin D, and antibodies against MIP-1alpha and monocyte chemoattractant protein-1 (MCP-1) abolished the stimulation of cell migration by TGF-beta1. These findings suggest that migration of these cells is regulated directly and indirectly via the expression of chemokines such as MIP-1alpha and MCP-1 mediated by RhoA in response to TGF-beta1. TGF-beta1 activated RhoA in the initial period, and thereafter inactivated them, suggesting that the inactivation of RhoA may be the cause of the reduced cell migration in response to TGF-beta1 at later times. We therefore attempted to elucidate the molecular mechanism of the inactivation of RhoA by TGF-beta1. First, TGF-beta1 phosphorylated RhoA via protein kinase A, leading to inactivation of RhoA. Second, wild-type p190 Rho GTPase activating protein (p190RhoGAP) reduced and DN-p190RhoGAP reversed the reduction of cell migration induced by TGF-beta, suggesting that it inactivated RhoA via p190 Rho GAP.
authors.affiliation: Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200-702, Korea.
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Kim
authors.forename: Jae-Gyu
authors.initials: JG
authors.lastname: Kim
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Moon
authors.forename: Chan-Young
authors.initials: CY
authors.lastname: Jeon
authors.forename: Ha-Young
authors.initials: HY
authors.lastname: Won
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yee-Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Seo
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Jaebong
authors.initials: J
authors.lastname: Kim
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
authors.forename: Pyeung-Hyeun
authors.initials: PH
authors.lastname: Kim
authors.forename: Jae-Bong
authors.initials: JB
authors.lastname: Park
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D015870:Gene Expression / Q000187:drug effects; D020662:Guanine Nucleotide Exchange Factors; D018922:HL-60 Cells; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: C074560:ARHGAP35 protein, human; C513043:ARHGAP5 protein, human; C513041:Arhgap35 protein, mouse; C513042:Arhgap5 protein, mouse; D002352:Carrier Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004268:DNA-Binding Proteins; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017868:Cyclic AMP-Dependent Protein Kinases; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein