Fibronectin regulates the activation of THP-1 cells by TGF-beta1.
OBJECTIVE
To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells.


METHODS
THP-1 monocytic cell line.


METHODS
THP-1 cells were primed for 48 h in the presence or absence of 250 pM TGF-beta1.


METHODS
Assays or assessments carried out, together with statistical test applied.


RESULTS
We found that adherence to fibronectin dramatically modulates the effects of TGF-beta1 on the human monocytic cell line THP-1. TGF-beta did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1beta-induced IL-8 secretion from suspended cells. In contrast, TGF-beta stimulated IL-8 secretion as well as augmented IL-1beta-induced IL-8 secretion from adherent cells. The differential effects of TGF-beta1 on IL-8 secretion from suspended and adherent cells could not be explained by differences in IL-1 receptor antagonist production. The effects of fibronectin on TGF-beta1 induced IL-8 secretion from THP-1 cells were mimicked by adhesion to immobilized anti-a4beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain.


CONCLUSIONS
These results indicate that alpha4beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.
Wang
A C
AC
Division of Pulmonary and Critical Care, VA Healthcare System, San Diego, CA 92161, USA. alwang@ucsd.edu
Fu
L
L
D002448:Cell Adhesion; D002460:Cell Line; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D005353:Fibronectins; C507763:IL1RN protein, human; D039041:Integrin alpha4beta1; D016023:Integrins; D053590:Interleukin 1 Receptor Antagonist Protein; D016209:Interleukin-8; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta