Interleukin-1beta 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-1beta. We demonstrated that mRNA for IL-1beta 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-1beta. A background level of IL-1beta 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, beta1 integrin, VLA4, (alpha)v(beta)3 (VNR), and ICAM-1 did not induce significant IL-1beta 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-1beta 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-1beta gene expression is greatly enhanced by the presence of immune complex.
Cobb
R R
RR
Department of Biology, Tanabe Research Laboratories, San Diego, CA 92121, USA.
Molony
J L
JL
D000936:Antigen-Antibody Complex / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D008024:Ligands; D009000:Monocytes / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000378:metabolism*; D015398:Signal Transduction
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D018821:CD18 Antigens; D019012:Integrin beta1; D039661:Integrin beta3; D007375:Interleukin-1; D016209:Interleukin-8; D008024:Ligands; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D017452:Receptors, IgG; D005340:Fibrinogen