Fibronectin regulates the activation of THP-1 cells by TGF-β1

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-I 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-beta1 did not significantly affect constitutive interleukin (IL)-8 secretion or IL-1 beta -induced IL-8 secretion from suspended cells. In contrast, TGF-beta1 stimulated IL-8 secretion as well as augmented IL-1 beta -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-alpha4 beta1 integrin antibody and to a fibronectin fragment containing the CS-1 domain. Conclusions: These results indicate that alpha4 beta1-mediated adhesion to fibronectin may play a key role during inflammation by profoundly influencing the effects of TGF-beta1 on monocytes.