Transforming growth factor beta enhances integrin expression and type IV collagenase secretion in human monocytes.
Transforming growth factor beta (TGF-beta), secreted within an inflammatory site or injected locally, induces leukocyte margination, chemotaxis, and accumulation. In addition to its potent direct chemotactic activity, TGF-beta may promote this leukocyte response by influencing cell surface integrin expression. At picomolar concentrations, TGF-beta increases steady-state mRNA levels for both the alpha 5 and the beta 1 chain of the fibronectin receptor in human blood monocytes. This increase in gene expression is reflected by selectively enhanced expression of alpha 5 (CDw49e), beta 1 (CDw29), and also alpha 3 (CDw49c) adhesion molecules on the cell surface. Functionally, TGF-beta 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-beta triggers transcriptional and posttranscriptional regulation of both the 92-kDa and the 72-kDa gelatinase/type IV collagenase. Thus, TGF-beta 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-beta may contribute to persistent leukocyte accumulation.
Laboratories of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
S M
SM
Wahl
J B
JB
Allen
B S
BS
Weeks
H L
HL
Wong
P E
PE
Klotman
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D016023:Integrins; D017469:Receptors, Fibronectin; D016212:Transforming Growth Factor beta; D017364:Collagenases; D020780:Matrix Metalloproteinase 9