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Fibronectin regulates the activation of THP-1 cells by TGF-beta1
1Division of Pulmonary and Critical Care, VA Healthcare System, San Diego, CA 92161, USA. alwang@ucsd.edu
Objective And Design:
To determine how fibronectin regulates the immunomodulatory effects of transforming growth factor (TGF)-beta on THP-1 cells.
Material Or Subjects:
THP-1 monocytic cell line.
Treatment:
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.