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PMID: 8506302 Published · ppublish English Journal Article

Transforming growth factor beta enhances integrin expression and type IV collagenase secretion in human monocytes.

Wahl SM, Allen JB, Weeks BS, Wong HL, Klotman PE

Abstract

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.

MeSH Terms
Amino Acid Sequence Cell Adhesion/drug effects Cell Membrane/metabolism Collagenases/metabolism Extracellular Matrix Proteins/chemistry,metabolism Fibronectins/metabolism Humans In Vitro Techniques Integrins/metabolism Matrix Metalloproteinase 9 Molecular Sequence Data Monocytes/metabolism Receptors, Fibronectin/metabolism Transforming Growth Factor beta/pharmacology
Chemicals
Extracellular Matrix Proteins Fibronectins Integrins Receptors, Fibronectin Transforming Growth Factor beta Collagenases Matrix Metalloproteinase 9
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wahl S M
Laboratories of Immunology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
Allen J B
Weeks B S
Wong H L
Klotman P E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1993-05-15
Pages
4577-81
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46555
Subset
IM
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