Figure 8.
Scheme of the activation and deactivation of macrophage migration in response to TGF-β1. (A) RhoA is activated in response to short-term treatment of TGF-β1 by an unknown mechanism, which induces expression of MIP-1α and MCP-1, probably via NF-κB and AP-1. These cytokines, as well as RhoA, may indirectly and directly, respectively, participate in stimulation of cell migration. (B) Long-term exposure to TGF-β1 inactivates RhoA via phosphorylation by PKA and activation of p190RhoGAP, resulting in inhibition of macrophage cell migration. This scheme shows dual function, in view of chemotaxis, of activation in early phase and deactivation of macrophages in late phase, which is mediated at least in part by RhoA activity.