Regulation of monocyte gene expression by the extracellular matrix and its functional implications.
By binding to extracellular matrix (ECM) proteins, integrins integrate signals from outside the cell and transmit them inwards, thereby providing cells with information about location and allowing them to respond to stimuli in a manner appropriate to their environment. This is particularly important for monocytes and macrophages, given their wide distribution throughout the body and the vital role they play in immune and inflammatory responses. Integrin-mediated interaction of monocytes with ECM is a potent regulator of gene expression and is strongly synergized by the presence of growth factors. This synergy between growth factors and integrins is also apparent in the overlap seen in their signaling pathways. Integrin-mediated interaction with ECM results in increased expression of numerous inflammatory and immune response genes, revealing an important role for ECM-integrin interaction in affecting monocyte function and thus impacting on the development of pathologies. This is of particular relevance in the context of immune and inflammatory responses, where integrin-mediated adhesive interactions with the ECM-rich peripheral tissues are central to the localization of both resident and infiltrating monocytes at inflammatory sites. Here, we will review the functional effects of integrin-ECM interactions on monocytes, with particular attention to the regulation of gene expression by ECM and its functional implications.
de Fougerolles
Antonin R
AR
Biogen Inc., Cambridge, Massachusetts 02142, USA. Tony_de_Fougerolles@Biogen.com
Koteliansky
Victor E
VE
D000818:Animals; D005109:Extracellular Matrix / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D015398:Signal Transduction
D016023:Integrins