Interleukin 10 regulates cellular responses in monocyte/endothelial cell co-cultures.
Adhesive interactions between monocytes and vascular endothelial cells increase the expression of the inflammatory genes, tissue factor (TF) and E-selectin, thus contributing to the inflammatory process. In this study, we have shown that these responses could be regulated by the immunomodulatory cytokine interleukin 10 (IL-10). IL-10 reduced TF generation in monocyte/endothelium co-cultures (64. 3 +/- 3.3% reduction, P < 0.01, n = 4) by acting directly on monocytes, whereas IL-4 inhibited TF expression in both monocytes and endothelium. Similarly, IL-10 reduced the induction of endothelial E-selectin by monocytes (100% reduction at 21 h), but had no effect on cytokine-induced E-selectin expression. IL-10 itself was not able to induce E-selectin protein or mRNA in endothelial cells. IL-10 mRNA was detected in monocytes after 6 h co-culture with endothelial cells, and was sustained for up to 30 h. Finally, IL-10 significantly reduced the adhesion of monocytes to endothelium (45% reduction), which may account in part for the inhibitory actions of IL-10. We conclude that IL-10 has an anti-inflammatory effect on monocyte/endothelium interactions, and may itself be produced as a result of such interactions.
Noble
K E
KE
Department of Haematology, Royal Free and University College Medical School, London, UK.
Harkness
D
D
Yong
K L
KL
D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013925:Thromboplastin / Q000378:metabolism
D019040:E-Selectin; D016328:NF-kappa B; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D013925:Thromboplastin