Interleukin-1β expression is induced by adherence and is enhanced by Fc-receptor binding to immune complex in THP-1 cells

Adherence of monocytes to endothelial cells and subsequently to basement membrane represents the initial steps in monocyte migration from the vasculature to the interstitium. We investigated the role of adhesion to endothelial cells and basement membrane in the induction of the cytokine IL-1β. We demonstrated that mRNA for IL-1β is induced in adherent THP-1 cells, but not in a matrix-specific manner. Adherence to fibrinogen, however, causes an increase in mRNA for IL-1β. A background level of IL-1β mRNA induction was observed in cells adherent to all matrices, including the non-specific human serum albumin substrate, as compared to non-adherent cells cultured in teflon troughs. In addition, antibodies to CD11a, CD11b, β 1 integrin, VLA4, αvβ3 (VNR), and ICAM-1 did not induce significant IL-1β mRNA when THP-1 cells were adherent to those immunoglobulins. THP-1 cells adherent to immune complexes of anti-CD11a, anti-CD11b, anti-VLA4, anti-VNR, and anti-ICAM-1 showed greater mRNA induction than cells adherent to primary antibodies alone. THP-1 cells adherent to non-specific immune complexes gave the highest level of mRNA induction. Secretion of IL-1β protein, measured by ELISA at 24 h, was greatest when cells were adherent to immobilized immune complexes or to fibrinogen. Our results demonstrate that a general adherence-induced increase in IL-1β gene expression is greatly enhanced by the presence of immune complex.