NDLI: Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction.

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Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction.

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Integrins as a primary signal transduction molecule regulating monocyte immediate-early gene induction.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yurochko, A. D. Liu, D. Y. Eierman, D. Haskill, S.
Description	Author Affiliation: Yurochko AD ( University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill 27599-7295.);
Abstract	Integrins are cell surface receptors found on monocytes that facilitate adhesion to both cellular and extracellular substrates. These integrins are thought to be involved in the selective gene induction observed after monocyte adhesion to various extracellular matrices. To investigate this hypothesis, we stimulated monocytes with monoclonal antibodies to different integrin receptors to specifically mimic the integrin receptor-ligand interactions. Engagement of the common beta chain of the beta 1 subfamily of integrins resulted in expression of the inflammatory mediator genes, interleukin 1 beta, interleukin 1 receptor antagonist, and monocyte adherence-derived inflammatory gene 6 (MAD-6), whereas engagement of the common beta chain of the beta 2 family did not. Furthermore, to characterize integrin-mediated gene induction, we examined the ability of antibodies to the alpha chain of integrin receptors to regulate gene expression. Engagement of the very late antigen 4 (VLA-4) receptor resulted in induction of all the mediator genes. Receptor crosslinking was required because individual Fab fragments were unable to stimulate gene induction whereas the divalent F(ab')2 fragment and the whole IgG molecule could. Interleukin 1 beta secretion was dependent on the anti-integrin antibody used. Some antibodies required a second signal and, for others, direct engagement was sufficient for protein production. In conclusion, engagement of integrin receptors regulated the production of both inflammatory mediator mRNA and protein. These results suggest that integrin-dependent recognition and adherence may provide the key signals for initiation of the inflammatory response during monocyte diapedesis.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Expression Regulation Integrins Physiology Monocytes Receptors, Very Late Antigen Signal Transduction Antibodies, Monoclonal Blotting, Northern Gene Expression Immunology Interleukin-1 Biosynthesis RNA Genetics Isolation & Purification RNA, Messenger Transcriptional Activation Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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