Transforming Growth Factor β Enhances Integrin Expression and Type IV Collagenase Secretion in Human Monocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 10; pp. 4577 - 4581
• Main Authors: Wahl, Sharon M., Allen, Janice B., Weeks, Benjamin S., Wong, Henry L., Klotman, Paul E.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.05.1993; National Acad Sciences
• Subjects: Amino Acid Sequence; Biological and medical sciences; Cell adhesion; Cell Adhesion - drug effects; Cell Membrane - metabolism; Cells; Collagenases - metabolism; Collagens; Enzymes; Extracellular matrix; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - metabolism; Fibronectins - metabolism; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Inflammation; Integrins; Integrins - metabolism; Leukocytes; Matrix Metalloproteinase 9; Messenger RNA; Molecular and cellular biology; Molecular Sequence Data; Molecules; Monocytes; Monocytes - metabolism; Receptors, Fibronectin - metabolism; Transforming Growth Factor beta - pharmacology; Human; Monocyte; Enzyme; Secretion; Transforming growth factor β; Cytokine; Inflammation; Gene expression; Adhesion; Chemotaxis; Integrin; Extracellular matrix; Metalloproteinase
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.10.4577

Transforming growth factor β (TGF-β), secreted within an inflammatory site or injected locally, induces leukocyte margination, chemotaxis, and accumulation. In addition to its potent direct chemotactic activity, TGF-β may promote this leukocyte response by influencing cell surface integrin expression. At picomolar concentrations, TGF-β increases steady-state mRNA levels for both the α5and the β1chain of the fibronectin receptor in human blood monocytes. This increase in gene expression is reflected by selectively enhanced expression of α5(CDw49e), β1(CDw29), and also α3(CDw49c) adhesion molecules on the cell surface. Functionally, TGF-β promotes, in a dose- and time-dependent fashion, monocyte adhesion to type IV collagen, laminin, and fibronectin. Potentially facilitating the movement of monocytes through the extracellular matrix, TGF-β triggers transcriptional and posttranscriptional regulation of both the 92-kDa and the 72-kDa gelatinase/type IV collagenase. Thus, TGF-β may play a pivotal role in the early phases of inflammation and repair through its ability to mediate monocyte adhesion, chemotaxis, and enzymatic digestion of extracellular matrix, whereas in chronic lesions, excess TGF-β may contribute to persistent leukocyte accumulation.