PMID- 16705092 OWN - NLM STAT- MEDLINE DCOM- 20061016 LR - 20220408 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 108 IP - 6 DP - 2006 Sep 15 TI - Transforming growth factor-beta1 regulates macrophage migration via RhoA. PG - 1821-9 AB - 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. FAU - Kim, Jun-Sub AU - Kim JS AD - Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Kangwon-Do 200-702, Korea. FAU - Kim, Jae-Gyu AU - Kim JG FAU - Moon, Mi-Young AU - Moon MY FAU - Jeon, Chan-Young AU - Jeon CY FAU - Won, Ha-Young AU - Won HY FAU - Kim, Hee-Jun AU - Kim HJ FAU - Jeon, Yee-Jin AU - Jeon YJ FAU - Seo, Ji-Yeon AU - Seo JY FAU - Kim, Jong-Il AU - Kim JI FAU - Kim, Jaebong AU - Kim J FAU - Lee, Jae-Yong AU - Lee JY FAU - Kim, Pyeung-Hyeun AU - Kim PH FAU - Park, Jae-Bong AU - Park JB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060516 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (ARHGAP35 protein, human) RN - 0 (ARHGAP5 protein, human) RN - 0 (Arhgap35 protein, mouse) RN - 0 (Arhgap5 protein, mouse) RN - 0 (Carrier Proteins) RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (DNA-Binding Proteins) RN - 0 (GTPase-Activating Proteins) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (RNA, Messenger) RN - 0 (Repressor Proteins) RN - 0 (TGFB1 protein, human) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Animals MH - Base Sequence MH - Carrier Proteins/genetics/metabolism MH - Cell Line MH - Cell Movement/drug effects/physiology MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Chemotaxis/drug effects/physiology MH - Cyclic AMP-Dependent Protein Kinases/metabolism MH - DNA-Binding Proteins MH - GTPase-Activating Proteins MH - Gene Expression/drug effects MH - Guanine Nucleotide Exchange Factors MH - HL-60 Cells MH - Humans MH - Macrophage Activation/drug effects/physiology MH - Macrophage Inflammatory Proteins/genetics/metabolism MH - Macrophages/*drug effects/*physiology MH - Mice MH - Models, Biological MH - RNA, Messenger/genetics/metabolism MH - Repressor Proteins MH - Transforming Growth Factor beta/*pharmacology MH - Transforming Growth Factor beta1 MH - rho GTP-Binding Proteins/metabolism MH - rhoA GTP-Binding Protein/*antagonists & inhibitors/physiology EDAT- 2006/05/18 09:00 MHDA- 2006/10/17 09:00 CRDT- 2006/05/18 09:00 PHST- 2006/05/18 09:00 [pubmed] PHST- 2006/10/17 09:00 [medline] PHST- 2006/05/18 09:00 [entrez] AID - S0006-4971(20)52552-4 [pii] AID - 10.1182/blood-2005-10-009191 [doi] PST - ppublish SO - Blood. 2006 Sep 15;108(6):1821-9. doi: 10.1182/blood-2005-10-009191. Epub 2006 May 16.