Macrophage migration is a key aspect in the initiation and progression of atherosclerosis Insulin-like growth factor (IGF)-1 is highly expressed in macrophages in human atheroma Its function in macrophage motility, however, remains to be elucidated The aim of this study was to investigate the impact of IGF-1 on macrophage migration, its signaling pathways and the involvement of integrins and/or matrix metalloproteinases (MMPs) Results Migration checker-box experiments demonstrated that IGF-1 induced chemotaxis in human THP-1/macrophages IGF-1 induced migration was inhibited by RGD-containing peptides and the alpha v beta 3-blocking antibody LM609, but was unaffected by the MMP-inhibitor GM6001 Immunoblotting demonstrated that IGF-1 did not affect the activation of MMPs or TIMPs, nor did it increase alpha v-integrin protein levels However, IGF-1 induced recruitment of alpha v beta 3, as well as trans-location of the integrin adaptor protein phospho-paxillin to focal adhesion sites Pharmacological blocking experiments with specific inhibitors of Akt, PKC and p38 MAP-kinase revealed that IGF-1-dependent activation of focal adhesion kinase (FAK) and paxillin, and consecutively IGF-1 facilitated migration, required IGF-1/IGF-1R-mediated PI3-kinase/PKC/p38-dependent integrin inside-out signaling Conclusion IGF-1 plays a vital role in macrophage migration critically implicated in tissue inflammation This involves activation of integrins and focal adhesion formation via inside-out PI3-kinase/PKC/p38-dependent signaling, but does not require MMP activation (C) 2010 Elsevier Inc All rights reserved